Diisopropylethyl-amine

The cyclization of 306 promoted by trimethylsilyl trifiate and diisopropylethyl-amine gives cw-dihydropyrones 307. Under these conditions methoxybutenone fails to form the aldol condensation product 305 (90TL2213). 

The reactions [OS 52], [OS 53], [OS 54] and [OS 55] were chosen as test reactions among a wide class of reagents employed for Michael additions. 1,3-Dicarbonyl compounds were chosen because of their relatively high acidity since they enable one to use weak bases instead of strong bases such as sodium efhoxide. The latter is labile to moisture and can react with the Michael acceptor [8]. Diisopropylethyl-amine was chosen as a weak base. 

Bode and co-workers have shown that the outcome of internal redox reactions is uniquely dependent on the base [111]. When diisopropylethyl amine is used in the reaction of an enol and an alcohol, the initially generated homoenolate is protonated... 

The hitherto preferred method for preparation of the butenolide is that of Price and Judge, which can be modified (by extraction of the bromolactone with methylene chloride and elimination of hydrogen bromide with triethylamine or preferably with diisopropylethyl amine in toluene at 70°C) to give routinely 60% or greater overall yield on a 6-mol scale. However, the large amount of... 

The replacement of the organic base diisopropylethyl amine with an equivalent amount of NaHC03 yielded the same product but with a yield of less than 10%. 

Abbreviations BAL, backbone amide linker BSA, bis(trimethylsilyl)acetamide DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene DCE, dichloroethane DCM, dichloromethane DIC, 2-diisopropylcarbodiimide DIEA, diisopropylethyl amine DMAP, A,A-dimethylaminopyr-idine DMF, dimethylformamide DMSO, dimethyl sulfoxide EDC, l-(3-dimethylaminopro-pyl)-3-ethylcarbodiimide hydrochloride HBTU, [0-(7-azabenzotriazol-l-yl)-l, 1,3,3-tetramethyluronium hexafluorophosphate MCPBA, m-chloroperoxybenzoic acid NMP, N-methylpyrrolidinone NMM, A-methylmorpholine PfP, pentafluorophenol RT, room temperature TFA, trifluoroacetic acid THF, tetrahydrofuran. 

This palladium-catalyzed three-component coupling reaction leading to the formation of aryl-substituted allylic amines was recently adapted to solid-phase synthesis (Scheme 8.23). Amines were chosen to attach to a solid support (Rink resin) in this three-component coupling process and were reacted with a variety of aryl halides and linear or cyclic non-conjugated dienes, the reaction being carried out at 100 °C for two days in the presence of palladium acetate and diisopropylethyl-amine. A wide variety of aryl-substituted allylic amines were then obtained after cleavage from the solid support by trifluoroacetic acid [60],... 

At present, the most convenient way for the preparation of 1,3-disubstituted azetidines involves the alkylation of a primary amine with the bis-triflate of a 2-substituted 1,3-propanediol species in the presence of diisopropylethyl-amine <2006JOC7885>. 

Stereocontrolled conjugate addition of lithium dimethylcuprate to the electron deficient 2,3-double bond of allenes 851 leads to 5,6-dihydropyranM-oncs 852 in moderate yield (Equation 343) <2000J(P1)3188>. Similarly, the Ag(l)-catalyzed intramolecular cyclization of the allenic acid 853 is accelerated upon addition of diisopropylethyl-amine to afford the 3,6-dihydropyran-2-one 854, an intermediate during the total synthesis of (—)-malyngolide (Equation 344) <2000JA10470>. 

SCHEME 14.1 Synthesis of lipids I and II by VanNieuwenhze et al. Bn, benzyl CDI, l,l -carbonyldiimidazole DBU, l,8-diazabicyclo[5.4.0]undec-7-ene DIPEA, diisopropylethyl-amine EDC, l-ethyl-3-(3-dimethylaminopropyl)carbodiimide NHS, A-hydroxysuccinimide Pyr, pyridine TFA, trifluoroacetyl Troc, 2,2,2-trichloroethoxycarbonyl. 

SYNTHESIS To a solution of 3.0 g 5-methoxytryptamine (see under melatonin for its preparation) in 20 mL sulfolane (tetramethylenesulfone) there was added 8.2 g diisopropylethyl amine and 10.7 g 2-iodopropane, and the two-phase mixture was heated on the steam bath with frequent shaking. After 3 h, the mixture was brought back to room temperature and stirred vigorously for an additional 16 h. After the removal of all volatiles under vacuum, the residue (30 g) was diluted with 100 mLH20, which gave a clear solution. The addition of 10 mL 5% aqueous NaOH produced a cloudy suspension that was extracted with... 

The Step 1 product (1.5 mmol) was dissolved in 10 ml benzene at 0°C and treated with phenylphosphonic dichloride (1.7 mmol), lH-tetrazole (8 mg), and N,N-diisopropylethyl amine (3.4 mmol). The mixture was then stirred at ambient temperature and a precipitate isolated after 15 minutes. The mixture was stirred for an additional 12 hours, then treated with 0.1ml methyl alcohol, and the mixture concentrated after an additional 4 hours of stirring. The residue was purified by chromatography with CHCl3/methyl alcohol/NH4OH, 9.5 0.5 0.02, and the product isolated in 89% yield as a mixture of diastereomers. 

The Step 1 product (4.0 mmol) dissolved in 20 ml DMF was treated with 3-hydroxy-l,2,3-benzotriazin-4(3H)-one (6.0 mmol) and diisopropylethyl amine (16.0 mmol), then cooled to 0°C. The mixture was then treated with l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.0 mmol), then stirred 30 minutes, and treated with the Step 3 product (4.0 mmol). This mixture was stirred 12 hours at ambient temperature, then concentrated in vacuo. The residue was diluted with 200 ml water, then extracted three times with 100 ml into CH2C12, and re-extracted with 100 ml HC1. The combined extracts were washed once with 100 ml apiece NaHC03 and brine solutions and used without further purification. 

A solution of the Step 6 product (0.22 mmol) in 2.5 ml DMF was treated with 3-hydroxy-1,2,3-benzotriazin-4(3H)-one (0.33 mmol) and diisopropylethyl amine... 

The preparation of the N(21)- and N(22)-substituted methyl corroles 2.196 and 2.197 has also been described, as have the N(21)- and N(22)-ethyl- and allyl-substituted species 2.198-2.203 (Scheme 2.1.67). Additionally, methylation reactions involving 3,17-carbethoxy corrole 2.102 and methyl iodide have been carried out using diisopropylethyl amine as the base. In this instance, in contrast to what happens in the all-P-alkyl series, the A(22)-methyl corrole 2.205 forms as the major product (by a nearly 2 1 margin over the N(21)-substituted alternative, 2.204) (Scheme 2.1.68). Interestingly, the same paper that describes this latter chemistry also reports an alternative synthesis of A(21)-methyl-3,17-carbethoxy corrole 2.204. In this approach, the thiaphlorin 2.101 was methylated using methyl iodide in diisopropylethyl amine to afford the N-methylated product 2.206 (Scheme 2.1.69). This latter species was then subject to a heat-induced sulfur extrusion. This gave the A(21)-methyl corrole 2.204 in 85% yield. A clear advantage of this stepwise procedure was that it allowed the A(21)-methyl-3,17-dicarbethoxy corrole 2.204 to be prepared selectively. 

Various trpentadienoic acids (57) by the mixed anhydride method (equation 37). The procedure is reproducible when V,V-diisopropylethyl-amine is used in place of triethylamine. 

F-HPLC to give 17 crude individual products 70-syn/anti and 71. These crude products were not isomerically pure. Removal of the fluorous tag and hydantoin formation was achieved by treatment of the individual amides 70-syn/anti and 71 with diisopropylethyl-amine (DIPEA) under microwave conditions. The cyclative cleavage reactions of 10-syn and 10-anti provided the same products 72. Normal-phase HPLC purification gave 11 of 12 possible final products 72 and 73. 

Ethyldiisopropylamine, (CH3)2CHNCH(CH3)2. Mol. wt. 129.24, b.p. 128°. Preparation from diisopropylamine and diethyl sulfate. Supplier Aldrich ( diisopropylethyl-amine ). 

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