ACETIC ACID, NITRO-, METHYL ESTER

Acetic acid, nitro-, methyl ester, 55, 77, 78 Acetic acid, trifluoro-, 55 70 Acetonitrile, diphenyl-, 55, 94, 102 Acetonitrile, diphenyl-2-(l-ethoxyethenyl)-[ Acetonitrile, diphenyl-2-(l-ethoxy-vinyl)-, 55, 102... 

Archer, owing to very unfortunate coincidences, had mistaken acid potassium tartrate for the acetylamino acid. Goldfarb et al. prepared authentic 5-acetylamino-2-thiophenecarboxylic acid, mp 230 232°C (methyl ester, mp 171-171.5°C ethyl ester, mp 161°C), through reduction of 5-nitro-2-thiophenecarboxylic acid with Raney nickel in acetic anhydride and proved the structure by Raney nickel desulfurization to 8-aminovaleric acid. They also confirmed that the acid mp 272-273°C (methyl ester, mp 135-136°C ethyl ester, mp 116-117°C) is 4-acetylamino-2-thiophenecar boxy lie acid as originally stated by Steinkopf and Miiller. The statement of Tirouflet and Chane that the acid obtained upon reduction and acetylation of 5-nitro-2-thiophenecarboxylic acid melts at 272°C must result from some mistake as they give the correct melting point for the methyl ester. 

Methyl 5-methoxyindole-2-acetate lndole-2-acetic acid, 5-methoxy-, methyl ester (8) 1H-lndole-2-acetic acid, 5-methoxy-, methyl ester (9) (27798-66-9) 5-Methoxy-2-nitrophenylacetic acid Acetic acid, (5-methoxy-2-nitrophenyl)- (8) Benzeneacetic acid, 5-methoxy-2-nitro- (9) (20876-29-3)... 

The synthesis of a triptan with a chiral side chain begins by reduction of the carboxylic acid in chiral 4-nitrophenylalanine (15-1). The two-step procedure involves conversion of the acid to its ester by the acid chloride by successive reaction with thionyl chloride and then methanol. Treatment of the ester with sodium borohy-dride then afford the alanilol (15-2). Reaction of this last intermediate with phosgene closes the ring to afford the oxazolidone (15-3) the nitro group is then reduced to the aniline (15-4). The newly obtained amine is then converted to the hydrazine (15-5). Reaction of this product with the acetal from 3-chloropropionaldehyde followed by treatment of the hydrazone with acid affords the indole (15-6). The terminal halogen on the side chain is then replaced by an amine by successive displacement by means of sodium azide followed by catalytic reduction of the azide. The newly formed amine is then methylated by reductive alkylation with formaldehyde in the presence of sodium cyanoborohydride to afford zolmitriptan (15-7) [15]. 

Nitro-phenyl)-acetic acid methyl ester (24)... 

To a solution of (4-nitro-phenyl)-acetic acid methyl ester 24 (8.11 g, 41.6 mmol) in ethanol (208 mL) was added 10% Pd/C (3.20 g) and NH4HCOO (14.0 g in 10 equal portions every 5 min) while stirring at room temperature. The reaction was stirred for 24 h, followed by... 

Nitrocoumarin and hydroxylamine in ethanol yield a 1 2 adduct (20) (see Section II,A,3) which with mineral acid cyclizes to 5-nitro-2,3-dihydro-indoxazene-3-acetic acid (63).21 With diazomethane, 63 yields the methyl ester and with acetic anhydride the JV-acetyl derivative. Oxidation to indoxazene-3-carboxylic acid is successful using selenium dioxide, whereas hydrogenation in the presence of palladium-charcoal brings about ring opening to j3-amino-j3-(2-hydroxy-5-nitrophenyl)propanoic acid. 

We also were successful in applying the alkyl nitrate nitration to TT-deficient heterocyclic compounds such as 2- and 4-meth-ylpyridines, 4-methyl pyrimidine, and to ir-excessive heterocyclics such as 2-methylbenzoxazole and 2-methylbenzothiazole (15). Both sodium and potassium amides in liquid ammonia were found to be effective as bases. In the KNH2-JI.NH3 system optimum yields are obtained if the molar ratio of base to substrate to nitrate ester is 2.0 1.0 2.5. After allowing 2-3 minutes for anion formation the nitrate ester is added as rapidly as possible while maintaining the temperature below -33°. Next the ammonia is replaced with ether and the nitro salt filtered off and acidified with aqueous acetic acid. 

Gyanomethyl N-benzoylglycinate refluxed 20-40 hrs. with 1.2 moles of p-nitro-phenylhydrazine in ethyl acetate -> hippuric acid p-nitrophenylhydrazide. Y 90%.—Similar reactions with the analogous methyl esters failed. F. e. s. P. Grud-zinska, Roczniki Ghem. 34, 1687 (1960). 

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