Triethylamine, reaction with dichloromethane

Thus, the unsubstituted starting compound 69 was treated with resorcinol in the presence of trifluoroacetic acid (TFA) to yield 70. Then, reaction of 69 with the cyclic a,/3-unsaturated ketone in the presence of lithium hydride gave the 7-substituted heteroaromatic compound 71, and ethyl cyanoacetate afforded the cross-conjugated product 72, whereas reaction with pyrimidine-2,4,6-trione in the presence of triethylamine yielded the addition product 73. Indole also been reacted with 69, and heating of the dichloromethane solution for 90 min in the presence of TFA yielded the addition product 74 in excellent yield (95%) <1998ZOR450> (Scheme 12). 

The reaction was performed in flame-dried modified Schlenk (Kjeldahl shape) flask fitted with a glass stopper or rubber septum under a positive pressure of argon. Trifluoromethanesulfonic anhydride (1.4 equiv) was added to a solution of giycosyl donor (0.191 mmol, 1 equiv) and diphenyl sulfoxide (2.8 equiv) in a mixture of toluene and dichloromethane (8 ml, 3 1 vol/vol) at — 78 °C. The reaction mixture was stirred at this temperature for 5 min and then at —40 °C for 1 h. At this time, 2-chloropyridine (5.0 equiv) and the giycosyl acceptor (3.0 equiv) were added sequentially at —40 °C. The solution was stirred at this temperature for 1 h, then at 0 °C for 30 min and finally at 23 °C for lh before the addition of excess triethylamine (10 equiv). The reaction was diluted with dichloromethane (100 ml) and was washed sequentially with saturated aqueous sodium bicarbonate solution (2 x 100 ml) and saturated aqueous sodium chloride (100 ml). The organic layer was dried (sodium sulfate) and concentrated. The residue was purified by silica gel flash column chromatography. 

The triethylamine hydrochloride formed in step (a) serves as an activator in step (b) for the reaction with an alcohol (ROH) providing the phosphite containing the desired protecting group. Acetonitrile proved to be a better solvent for this reaction than dichloromethane. It was found that activation by pyridinium hydrochloride was faster but led to formation of dinucleoside phosphite. 

Rink resin derived imines have been reported to give cycloaddition reactions with acetyl chlorides (or equivalent) using triethylamine as the base and dichloro-methane as the solvent at temperature ranging from 0°C to room temperature [70], The resin-bound p-lactam could be cleaved by using 50% trifluoroacetic acid (TFA) in dichloromethane, to afford the /V-unsubstituted p-lactam. 

Even very mild electrophiles may become involved in these reactions. Although triethyl-amine does not normally react with dichloromethane, in the presence of certain platinum ) salts quaternisation occurs and the salt [Et3NCH2Cl]2[PtCl4] may be isolated. The precise mechanism of these reactions is not known, but it seems likely that electrophilic attack upon a co-ordinated triethylamine is the key step. Notice that a tertiary amine, which cannot undergo competing deprotonation reactions, is involved in the reaction. 

Enantiopure fused oxopiperazino-/3-lactams have been produced by application of the Staudinger reaction with 5,6-dihydropyrazin-2-(l/7)-ones and the /3-lactams were converted to the 2-oxopiperazine-3-acetic acid esters in good yield with no epimerization (Equation 86) <2006TL8911>. Fused /3-lactams have been formed from macrocyclic imines by use of the Staudinger reaction (see Section 2.04.9.7). When phenoxyacetyl chloride and triethylamine were used, the best yields (45-52%) of the fused /3-lactams were obtained with dry dichloromethane as solvent <2006TL8855>. 

To a stirred mixture of 208 mg (1.00 mmol) of 86, 14 mg (0.02 mmol) of Pd(PPh3)2Cl2 and 7 mg (0.04 mmol) of Cul in a mixture of 5 mL of THF and 1 mL of triethylamine under nitrogen was added dropwise over 10 min a solution of 0.13 mL (1.10 mmol) of 85 in 5 mL of THF. The reaction mixture was stirred at room temperature for 6 h until the complete consumption of 86 (monitored by TLC or GC-MS). Then, a solution of 0.17 mL (2.00 mmol) of pyrrolidine in 5 mL of methanol was added and the mixture was heated at reflux for 6 h until the complete conversion of the intermediate alkyne (monitored by TLC or GC-MS). The solvents were evaporated in vacuo and the residue was chromatographed over a short pad of aluminum oxide, eluting with dichloromethane, to furnish after recrystallization from hexane-chloroform 200 mg (71 %) of the analytically pure enamine 87e as crystals with a blue metallic luster, m.p. 100-101 °C. 

The key step in a short synthesis of ( )-tylophorine77 is an intramolecular double conjugate addition reaction. Reaction of the ( , )-unsaturatcd ester 1 (R2 = 8-phcnylmcnthyl) with ferf-butyldimethylsilyl triflate in the presence of excess of triethylamine in dichloromethane produces an 80 20 inseparable mixture of the indolizidines 2A and 2B78. Treatment of a mixture of 2A and 2B (R2 = 8-phenylmethyl) with sodium hydride in refluxing tetrahydro-furan for 2.5 hours gives the single indolizidine 2 A. Dioxanyl ester 1 furnishes, on reaction with... 

Treatment of the selenides 165 with /ftt-butyl hypochlorite in a dichloromethane solution followed by reaction with triethylamine yielded the enantiomerically pure spiroselenuranes 166 (Equation 43) <1998TA3303>. 

A mixture of spermine (8 g, 39.5 mmol, 1 eq) and triethylamine (33 ml, 237 mmol, 6 eq) in dichloromethane (75 ml) was cooled to 0°C in an ice bath. A solution of trifluoroacetic anhydride (41.5 g, 198 mmol) in dichloromethane (100 ml) was added dropwise over 1 h. The reaction medium was stirred overnight at room temperature, then neutralized by addition of sodium hydrogen carbonate solution (75 ml, 5% ww) (see Note 5). The aqueous phase was extracted with dichloromethane (3x150 ml) and the combined organic phases washed with potassium hydrogen sulfate (3x100 ml, 0.5 M), brine and dried over magnesium sulfate. Concentration yielded (14) as a yellowish powder (22.5 g, 97%). 

To a solution of this silyl ether 24 (0.1 mmol) in benzotrifluoride (BTF) (4mL) were added a nitroalkane (0.99 mmol), phenyl isocyanate (1.98 mmol), and two drops of triethylamine. The reaction mixture was stirred at 25 °C for 3 days. After removal of the solvent, the residue was purified by three-phase extraction with FC-72 (20 mL), benzene (20 mL), and water (20 mL). The combined fluorous extracts were concentrated to yield the iso-xazolines 25, which were dissolved in diethyl ether (3 mL) at 25 °C. HF pyridine (0.1 mL) was added and the solution was stirred for 1 h at 25 °C. After removal of the solvent, the residue was redissolved in dichloromethane (20 mL). Saturated aqueous NH4CI (10 mL) was added and the organic/aqueous biphase was washed twice with FC-72 (10 mL). After separation of the layers, the aqueous phase was extracted twice with dichloromethane and the combined organic phases were dried (MgSO4) and concentrated to yield the deprotected isoxazoline 26. 

Prepare a solution of allyl bromide (1.0 mL, 1.4 g, 12 mmol) in dry diethyl ether (10 mL) and add it dropwise to a stirred solution of aza[15]crown-5, 16, (2.6 g, 12 mmol) and triethylamine (1.8 mL, 1.3 g, 13 mmol) in dry diethyl ether (25 mL) at room temperature under an inert atmosphere. Triethylamine hydrochloride precipitation occurs almost immediately but it is worth stirring the reaction mixture for several hours more to ensure complete reaction. Remove the solvent by rotary evaporation and add distilled water (25 mL) to dissolve the precipitate. Extract with dichloromethane (3 x 25 mL) and remove the organic solvent by rotary evaporation. Distil the resulting pale green oil by Kugelrohr (b.p. 118-120 °C, 0.25 mmHg) to yield /V-allylaza[ 15]crown-5 (18) as a colourless oil. 

A differently anchored Mukaiyama reagent is the N-methylpyridinium iodide salt 57 [71], which has been obtained by reaction of the Merrifield resin with N-Boc-aminocaproic acid in the presence of cesium carbonate to give the supported ester 55 (Scheme 7.19). Further Boc-deprotection and reaction with 6-chloronicoti-noyl chloride in the presence of Hxinig s base furnished the anchored 2-chloro-pyridine 56, which was transformed into the final N-methylpyridinium salt 57 after N-methylation in neat methyl iodide. This supported reagent has been used in the rapid microwave-assisted esterification of carboxylic acids and alcohols in the presence of triethylamine as base, with dichloromethane as solvent at 80 °C, the products being obtained in high purity after simple resin filtration [72],... 

Alkenylaminoboranes (14), though not in the category of alkenyloxyboranes, also undergo aldol reactions with carbonyl compounds (Scheme 13). Pure alkenylaminoboranes can be isolated from the reaction of a ketimine, boron trichloride and triethylamine in dichloromethane. ... 

As a result of easy access to perfluoroalkanesulfonyl fluorides in recent years, variety of esters have been synthesized by their reactions with fluorinated alcohols and phenols. The first example is the preparation of polyfluoroalkyl triflates, reported by Burdon and McLaughlin, who carried out the reaction in the presence of one equivalent of triethylamine in dichloromethane at — 30 °C91 (equation 60). Excessive base had to be avoided in the reaction, otherwise the nonvolatile quaternary ammonium salt, instead of the desired triflate, was obtained. 

Selective trifluoroacetylation of primary amines in the presence of secondary amines can be accomplished by reaction with a stoichiometric amount of ethyl trifluoroacetate (bp 60-62 C) in THF, acetonitrile or dioxane at 0 C. The product is simply isolated by evaporation of the solvent and liberated ethanol. " Perhaps the most common method entails acylation of the amine with trifluoro-acetic anhydride in the presence of a suitable base such as triethylamine or pyridine in dichloromethane [Scheme 8.26]. New reagents for the N-trifluoro-acetylation of amines include -(trifluoroacetyl)succinimide, a solid and storable reagent, /V-(trifluoroacetoxy)succinimide, which must be stored in a frozen benzene matrix, and l-(trifluoroacetyl)-l,2,3-benzotriazole. The latter reagent is a stable, crystalline reagent (mp 89-91 C) prepared in quantitative... 

In a similar fashion, resin-bound imines 109 were employed to prepare a library of structurally diverse P-lactams by [2+2] cycloaddition reactions with different ketenes. Thus, as shown in Scheme 4.1.22, amino acids tethered to the acid labile Sasrin resin (103) were condensed quantitatively to imines 109 by using a large excess of alkyl, aryl, or a,P-unsaturated aldehydes in a mixture of trimethylorthoformate and dichloromethane. Optimisation studies of the [2+2] cycloaddition step, showed that conversion to P-lactams 110 could only take place by slow addition of acid chlorides to a suspension of the imine resin at 0°C in the presence of triethylamine. By using a large excess of ketene at high concentration, the cycloaddition of imines derived from even sterically hindered amino acids [e.g. valine) could be carried out with full conversion. After mild TFA cleavage from the resin and preparative HPLC purification, the p-lactams 111, 112 were isolated in yields of 55-97%. 

The synthesis of formaldehyde dithioacetals may be achieved through a reaction with thiols and dichloromethane in the presence of Wilkinson s catalyst and triethylamine (eq 83). The reaction is simple and takes place under very mUd reaction conditions. 

The best alkylating agents for silyl enol ethers are tertiary alkyl halides they form stable carbocations in the presence of Lewis acids such as TiCl4 or SnCl4. Most fortunately, this is just the type of compound that is unsuitable for reaction with lithium enolates or enamines, as elimination results rather than alkylation a nice piece of complementary selectivity. Below is an example the alkylation of cyclopentanone with 2-chloro-2-methylbutane. The ketone was converted to the trimethylsilyl enol ether with triethylamine and trimethylsilylchloride we discussed this step on p. 466 (Chapter 20). Titanium tetrachloride in dry dichloromethane promotes the alkylation step. 

To a solution of 250 mg l-phenylseleno-2-trimethylsilylethene (1.0 mmol) in 2.4 mL dichloromethane was added 0.173 mL SnCU (391 mg, 1.5 mmol) followed by 312 mg 2-p-toluenesulfonylacrylate (1.3 mmol) at —78°C. The mixture was stirred at —78°C for 3 h. The reaction mixture was quenched by 0.32 mL triethylamine (230 mg, 2.3 mmol) and then with saturated aqueous NaHCOs. The mixture was extracted with dichloromethane, and the organic phase was washed with water, dried over Na2S04, and evaporated in vacuo. The residue was purified by column chromatography over silica gel eluting with hexane/ether (2 1) to give 278 mg methyl / -l-(p-toluenesulfonyl)-c-2-[(phenylseleno)-(trimethylsilyl)methyl]-l-cyclopropanecarboxylate, in a yield of 56%. An analytically pure sample was recrystallized from hexanes/ether as colorless crystals, m.p. 117-119°C. 

A solution of ethyl 4-iodobenzoate (210, 276 mg, 1 mmol), pinacol borane (351, 190 mg, 1.5 mmol, 1.5 eq.) and triethylamine (0.42 ml, 0.30 g, 3 mmol, 3 eq.) in dioxane (4 ml) was flushed with nitrogen, and Pd(dppf)Cl2 (22 mg, 3 mol%) was added. The reaction mixture was stirred at 80 C under a nitrogen atmosphere for 2 h. After being cooled, the reaction mixture was poored into water (20 ml) and extracted with dichloromethane (3x20 ml). Combined organic layers were washed with water and brine, dried (Na2S04), filtered, and evaporated. From the crude product, 218 mg (79%) of pure 4-ethoxycarbonylphenyl pinacolboronate (367) was obtained. 

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