反应详情

温度

16.5 °C

A 5 L, 4-necked, round-bottomed flask, equipped with a mechanical stirrer, digital thermometer and nitrogen inlet-outlet, is charged with 102.39 g of (2R)-2-(hydroxymethyl)hexanoic acid, 123.0 g of O-benzylhydroxylamine hydrochloride and 2.25 L of water. Adjust the pH by adding one equivalent of NaOH to a pH of 4-5. Stir the reaction mixture at 18° C.±3° C. (external temperature: 15-18° C.) for 30 minutes to give a cloudy solution. Add 161.3 g of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (EDCl) over a period of 60 minutes in 6 portions, while maintaining the internal temperature at 18° C.±3° C. (external temperature: 10° C.±3° C.). Wash the funnel once with 50 mL of water. Stir the thick suspension at 20° C.±3° C. for 2 hours. Filter the solids through a polypropylene filter cloth and a Büchner funnel then wash the flask and filter cake once with 0.5 L of water. Air-dry the cake at 20° C.±3° C. (house vacuum) for 2 hours, then dry the wet cake (˜265 g weight) at 65° C.±3° C. (15 mbar) for 24 hours to give 162 g of (2R)-2-(hydroxymethyl)-N-(phenylmethoxy)hexanamide (C3) as a white solid in 95% yield. m.p. 100-102° C.; [α]D25=+0.556 (c, 1.0, MeOH).

1. customA 5 L, 4-necked, round-bottomed flask, equipped with a mechanical stirrer
2. customto give a cloudy solution
3. temperaturewhile maintaining the internal temperature at 18° C.±3° C. (external temperature: 10° C.±3° C.)
4. washWash the funnel once with 50 mL of water
5. stirringStir the thick suspension at 20° C.±3° C. for 2 hours
6. filtrationFilter the solids through a polypropylene
7. filtrationfilter cloth
8. washa Büchner funnel then wash the flask
9. filtrationfilter cake once with 0.5 L of water
10. customAir-dry the cake at 20° C.±3° C. (house vacuum) for 2 hours
11. customdry the wet cake (˜265 g weight) at 65° C.±3° C. (15 mbar) for 24 hours