2- Benzyl-6-ethoxycarbonyl

Benzyl-2(l//)-phthalazinone (41, R = H) gave 4-benzyl-2-ethoxycarbonyl-methyl-l(2//)-phthalazinone (41, R = CH2C02Et) (ClCH2C02Et, NaOH, EtOH, 95°C, 1 h 87%) 2-ethoxycarbonyImethy 1-4-phenyl-l(2//)-phthala-... 

Thieno[2,3-c]pyridine, 2-amino-6-benzyl-3-ethoxycarbonyl-4,5,6,7-tetrahydro-biological activity, 4, 1015 Thieno[2,3-c]pyridine, 4,5,6,7-tetrahydro-biological activity, 4, 1015 Thieno[3,2-6]pyridine, 3-hydroxy-synthesis, 4, 1010... 

Interestingly, a reverse isomerization (1,4-dihydro 1,2-dihydro) was observed when a 1,4-dihydroquinoline derivative was obtained by the reaction of lithiated l-ethoxycarbonyl-l,2-dihydroquinoline-2-phosphonate 36 with benzyl bromide... 

Treatment of 8-[(4-cyanophenyl)methoxy]-7-formyl-2-cyclopentyl-2,3,4,6,11,1 la-hexahydro-l//-pyrazino[l,2-i]isoquinoline-l,4-dione with (Et0)2P(0)CH2C00Et and NaH in THF at 40 °C overnight, or with (2-pyridylmethyl)-, 4-[(ethoxycarbonyl)benzyl]-, (4-nitrobenzyl)-, and (meth-oxymethyl)triphenylphosphonium halogenide in the presence of KH in THF at room temperature gave 7-ethylene derivatives 386 (98MIP7). 

A solution of 1-benzyl-4-piperidone, ethyl cyanoacetate, powdery sulfur and morpholine in ethanol is heated moderately under reflux for about 20 minutes to dissolve the powdery sulfur. The mixture is heated under reflux for one further hour to complete the reaction. On standing at room temperature, the mixture yields a precipitate. The precipitate is collected by filtration, washed well with methanol and recrystallized from methanol to give 2-amino-6-benzyl-3-ethoxycarbonyl-4,5,6,7-tetrahydrothieno(2,3-c)-pyridine as almost colorless needles melting at 112° to 113°C. 

Because the olefin geometry in compound 9 will most certainly have a bearing on the stereochemical outcome of the hydroboration step, a reliable process for the construction of the trans trisubsti-tuted olefin in 9 must be identified. A priori, the powerful and predictable Wittig reaction28 could be used to construct E u, [3-unsaturated ester 10 from aldehyde 11. Reduction of the ethoxycarbonyl grouping in 10, followed by benzylation of the resulting primary alcohol, would then complete the synthesis of 9. Aldehyde 11 is a known substance that can be prepared from 2-furylacetonitrile (12). 

A Wittig-type reaction of iminophosphorane 995 with benzoyl and ethoxycarbonyl isocyanates gave (91T6747) thiadiazolotriazines 996, whereas reaction of 995 with aromatic isocyanates afforded 997. On the other hand, iminophosphorane 995 reacted with methyl and benzyl isothiocyanates to give 998. Reaction of 995 with acid chlorides gave 999 (88H1935). All these compounds display mesoionic or zwitter ionic character (Scheme 184). 

C22H24N2O3S2 124492-03-1) see Spirapril A -[l(8)-ethoxycarbonyl-3-phenylpropyl]-L-alanine benzyl ester... 

Ethoxycarbonyl chloride is, by virtue of resonance involving the ester function, less reactive than acetyl chloride, and the reagent has found application for selective O-acylation in the steroid field.34 With this reagent, methyl 4,6-O-benzylidene-a-D-glucopyranoside yielded35 2- and 3-esters in the ratio 24 1, and the related benzyl-thiocarbonyl chloride gave the 2-ester in 58% yield.36... 

Racemic fra .s-A--benzyl-2.5-bis-(ethoxycarbonyl)pyrrolidine has been resolved via its dicarboxylic acid, followed by subsequent transformation to offer (2R,5R)-21 or (25,5S -21. The absolute configuration of the alkylated carboxylic acids indicates that the approach of alkyl halides is directed to one of the diastereotopic faces of the enolate thus formed. In the following case, the approached face is the 57-face of the (Z)-enolate. By employing the chiral auxiliary (2R,5R)-21 or its enantiomer (25.55)-21. the (/ )- or (S)-form of carboxylic acids can be obtained with considerably high enantioselectivity (Table 2-4). 

Pd-catalyzed alkoxycarbonylation enables synthesis of a variety of heterocyclic esters that are otherwise not easily prepared. 5-Bromopyrimidine was transformed into 5-ethoxycarbonyl-pyrimidine in quantitative yield employing the Pd-catalyzed alkoxycarbonylation. The alkoxycarbonylation of 2-chloro-4,6-dimethoxypyrimidine, in turn, led to benzyl 4,6-dimethoxypyrimidine-2-carboxylate (112), whereas alkoxycarbonylation of 2-(chloromethyl)-4,6-dimethoxypyrimidine provided pyrimidinyl-2-acetate 113 [79]. 4,6-Dimethoxypyrimidines 112 and 113 are both important intermediates for the preparation of antihypertensive and antithrombotic drugs. 

N-Debenzylation oft-amines.1 The reagent converts N-benzyl tertiary amines into the corresponding (3-(trimethylsilyl)ethoxycarbonyl derivatives, which are cleaved by fluoride ion (8, 470-471) to sec-amines. 

To overcome these difficulties in the selective deprotection and chain extension, several carboxyl-protecting groups, namely, allyl (16,32), benzyl (43,44), tert-butyl (42), 2-bromoethyl (45), 2-chloroethyl (45), heptyl (46), 4-nitrophenyl (47,48), and pentafluorophenyl (49) for L-serine/L-threonine have been introduced or applied. Similarly, amino-protecting groups for L-serine/L-threonine that have proved useful for the synthesis of glycopeptides are tm-butyloxycarbonyl (50), 9-fluorenylmethoxycarbonyl (43,44,48), 2-(2-pyridyl)ethoxycarbonyl (51), 2-(4-pyridyl)ethoxycarbonyl (44,52), and 2-triphenylphosphonioethoxycarbonyl (53). Some applications of these groups have been discussed in earlier reviews (7-11). 

Experimental Procedure 4.2.5. Ammonium Ylide Formation and Stevens Rearrangement Diethyl 2-Benzyl-2- [(ethoxycarbonyl)mefiryl](methyI)amino malo-nate [1241]... 

The amidic group in methyl A -acetyl-p-aminobenzoate was reduced preferentially to an ester group with borane in tetrahydrofuran (1.5-1.8 mol per mol of the amide), giving 66% yield of methyl p-A -ethylaminobenzoate. Similarly l-benzyl-3-methoxycarbonyl-5-pyrrolidone afforded methyl l-ben2yl-3-pyr-rolidinecarboxylate in 54% yield and l,2-diethyl-5-ethoxycarbonyl-3-pyra-zolidone gave ethyl l,2-diethylpyrazolidine-3-carboxylate in 60% yield. 

Enalapril Enalapril, (S)-l-[iV-[l-(ethoxycarbonyl)-3-phenylpropyl]-L-alanyl]-L-proline (22.7.12), is synthesized by reacting the benzyl ester of L-alanyl-L-proline with the ethyl ester of 3-benzoylacrylic acid, which forms the product 22.7.11, the reduction of which with hydrogen using a Raney nickel catalyst removes the protective benzyl group, giving the desired enalapril (22.7.12) [24], Alternative methods of syntheses have also been proposed [25-29]. 

To Boc-Ala-f/V-(4- 4-[2-(trimethylsilyl)ethoxycarbonyl]butoxy]benzyl)]Ile-OAI (2.0 g, 2.82 mmol) in THF (20 mL) was added under stirring at rt 1 M TBAF in THF (3 mL) dropwise, and saponification of the ester proceeded for 3 h. The H20 (100 mL) and AcOH (3 mL) were added to the mixture. The acid was extracted into EtOAc and the combined EtOAc extracts were washed with brine and H20, and dried (MgS04). The solvent was removed, and the resulting oil was purified by preparative HPLC (C18, 2.2 x 25 cm 0-60% MeCN over 60 min) to give a colorless oil yield 2.54 g (44%) (note this is the yield given in the original paper, clearly it is incorrect). 

The well-known application of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine as a diene in inverse electron demand Diels-Alder cyclizations was adapted for the synthesis of purines <1999JA5833>. The unstable, electron-rich dienophile 5-amino-l-benzylimidazole was generated in situ by decarboxylation of 5-amino-l-benzyl-4-imidazolecarboxylic acid under mildly acidic conditions (Scheme 54). Collapse of the Diels-Alder adduct by retro-Diels-Alder reaction and elimination of ethyl cyanoformate, followed by aromatization by loss of ammonia, led to the purine products. The reactions proceeded at room temperature if left for sufficient periods (e.g., 25 °C, 7 days, 50% yield) but were generally more efficient at higher temperatures (80-100 °C, 2-24 h). The inverse electron demand Diels-Alder cyclization of unsubstituted 1,3,5-triazine was also successful. This synthesis had the advantage of constructing the simple purine heterocycle directly in the presence of both protected and unprotected furanose substituents (also see Volume 8). 

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