Sodium Bicarbonate → (2S)-2-{[(benzyloxy)carbonyl]amino}-2-(4-methoxyphenyl)acetic acid

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반응 단계

A suspension of NaHCO3 (184 mg, 2.2 mmol), commercially available N-(benzyloxycarbonyloxy)succinamide (548 mg, 2.2 mmol) and (S)-α-amino-4-methoxybenzeneacetic acid (360 mg, 2 mmol), synthesis described in U.S. Pat. No. 3,517,023, in 1:1 acetone/H2O was stirred for 18 hours at 20° C. After partial concentration and extraction with CH2Cl2, the pH was adjusted to 1.5 and the solution extracted with EtOAc (3×). The EtOAc extracts were washed with brine, dried over MgSO4 and concentrated to yield (S)-α-[N-[(phenylmethoxy)carbonyl]amino]-4-methoxybenzeneacetic acid. A solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.HCl (608 mg, 3.2 mmol), hydroxybenztriazole (643 mg, 4.76 mmol) and (S)-α-[N-(phenylmethoxy)carbonyl]amino-4-methoxybenzeneacetic acid (1 g, 3.17 mmol) in CH2Cl2 (10 mL) was stirred one hour at 0° C. whereupon N-methylmorpholine (0.7 mL, 6.4 mmol) and t-butylamine (0.5 mL, 4.8 mmol) were added and the reaction stirred at 20° C. for 18 hours. The reaction was diluted with EtOAc, washed with H2O, aq. NaHCO3, brine, dried over MgSO4, and concentrated. Pure (S)-N-(1,1-dimethylethyl)-α-[N-[(phenylmethoxy)carbonyl]amino]-4-methoxybenzeneacetamide was obtained after chromatography on silica gel using 35% EtOAc/hexane as eluant. Hydrogenation of (S)-N-(1,1-dimethylethyl)-α-[N-[(phenylmethoxy)carbonyl]amino]-4-methoxybenzeneacetamide over 10% Pd(OH)2 /C at 1 atom of H2 in 1:1 MeOH/EtOAc generated the title compound which required no further purification following filtration and concentration.

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