Sodium borohydride → HCID 58859730, compound

Temperature

-10 °C

A clean, dry flask was charged with (S)-(3-phenylamino-butyryl)-carbamic acid benzyl ester (0.821 g, 2.63 mmol) followed by reagent grade ethanol (20 mL) and cooled to −10° C. Sodium borohydride (0.070 g, 1.84 mmol) was added to the solution in one portion. Nitrogen gas purging is maintained for 5 minutes. A solution of 3.3 M aqueous magnesium chloride solution (0.561 g MgCl2 6H2O in 1.5 mL water) was added at such a rate that the internal temperature did not exceed −5° C. Once addition was completed, the reaction solution was warmed to 0° C. for 30 min. The reaction was quenched with methylene chloride (10 mL), and 1 M hydrochloric acid/citric acid solution (10.52 mL 1 N HCl, and 1.38 g citric acid). This bilayer was stirred at room temperature for six hours. The reaction mixture was diluted with ethyl acetate (200 mL) and neutralized with sat. aqueous NaHCO3 solution (pH=10). The organics were collected together and washed with sat. NaCl solution and dried over Na2SO4, filtered and concentrated. Flash chromatography using an Isco system (100% hexane to 50% EtOAc/50% hexane gradient) afforded the title compound (0.733 g). (91%).

1. customA clean, dry flask
2. customNitrogen gas purging
3. temperatureis maintained for 5 minutes
4. additionA solution of 3.3 M aqueous magnesium chloride solution (0.561 g MgCl2 6H2O in 1.5 mL water) was added at such a rate that the internal temperature
5. customdid not exceed −5° C
6. additionOnce addition
7. temperaturethe reaction solution was warmed to 0° C. for 30 min
8. customThe reaction was quenched with methylene chloride (10 mL), and 1 M hydrochloric acid/citric acid solution (10.52 mL 1 N HCl, and 1.38 g citric acid)
9. additionThe reaction mixture was diluted with ethyl acetate (200 mL)
10. customThe organics were collected together
11. washwashed with sat. NaCl solution
12. dry with materialdried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated

ORD record

ord-78c8ee5d4b2b4815abd0fa19411ab3ed

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07504508B2