Sulfuric Acid → N-[1(S)-Ethoxycarbonyl-3-phenylpropyl]-L-alanine

Temperature

20 °C

N-(1-ethoxycarbonyl-3-oxo-3-phenylpropyl)-L-alanine [(1S/1R)=9.0] (10.0 g, 34 mmoles) was added to 105 ml of 7% (w/w) water-containing ethanol containing 1.9 N sulfuric acid. Thereto 50% (w/w) water-containing 5% Pd--C (5.0 g) was added and the catalytic reduction was carried out in hydrogen atmosphere (atmospheric pressure) under the conditions of an inner temperature of about 20° C. and an agitation power of a range from 0.5 to 1 kW/m3 (amount of sulfuric acid based on substrate: 6 equivalents). Supply of hydrogen was stopped at the time when hydrogen is absorbed in 90% and somewhat more of the required amount. And then, the atmosphere was rapidly replaced with nitrogen to stop the reaction. Pd--C was rapidly removed by filtration and the Pd--C cake was conscientiously washed with 10 ml of 7% (w/w) water-containing ethanol and 5 ml of water. After 30 ml of water was added to the resulting filtrate, the filtrate was neutralized (pH 4.5) by slowly adding dropwise an aqueous 30% (w/w) sodium hydroxide solution. The filtrate was concentrated at the inner temperature of a range from 40° to 60° C. under reduced pressure, and then concentrated under reduced pressure with appropriately adding water to obtain slurry with replacing with water. The content of ethanol in the slurry was 3% (w/w), the content of sodium sulfate was 9% (w/w) and the pH was 5.0. After cooling to an inner temperature of 20° C., the crystal was filtered and washed with water in a 2-fold amount of the cake. The resulting crystal was vacuum-dried (30 mmHg to 0.1 mmHg) at a range from 40° to 60° C. to obtain N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine (6.3 g, 23 mmoles). The yield was 75%. HPLC purity: 99.3% (w/w), the content of N-(1(R)-ethoxycarbonyl-3-phenylpropyl)-L-alanine: not detected, the content of N-(1-ethoxycarbonyl-3-cyclohexylpropyl)-L-alanine: 0.1% (w/w), the content of N-(1-carboxy-3-phenylpropyl)-L-alanine: less than 0.1% (w/w), residue on ignition: 0.1% 35 (w/w).

1. additionwas added
2. customunder the conditions of an inner temperature of about 20° C.
3. customis absorbed in 90%
4. customthe reaction
5. customPd--C was rapidly removed by filtration
6. washthe Pd--C cake was conscientiously washed with 10 ml of 7% (w/w) water-
7. additioncontaining ethanol and 5 ml of water
8. additionAfter 30 ml of water was added to the resulting filtrate
9. additionby slowly adding dropwise an aqueous 30% (w/w) sodium hydroxide solution
10. concentrationThe filtrate was concentrated at the inner temperature of a range from 40° to 60° C. under reduced pressure
11. concentrationconcentrated under reduced pressure with appropriately adding water
12. customto obtain slurry
13. filtrationthe crystal was filtered
14. washwashed with water in a 2-fold amount of the cake
15. customThe resulting crystal was vacuum-dried (30 mmHg to 0.1 mmHg) at a range from 40° to 60° C.

ORD record

ord-8b4049ae76cf411988a77a9496302884

Source dataset

uspto-grants-2000_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06118010