Benzyl chloroformate → (S)-(3-Phenylamino-butyryl)-carbamic Acid Benzyl Ester

Temperature

-10 °C

A clean, dry and nitrogen gas purged flask was charged with (S)-3-phenylamino-butyramide (3.25 g, 0.018 mmol) in THF (65 mL) and the mixture was cooled to −10° C. Benzyl chloroformate (3.12 mL, 0.022 mmol) was then added followed by the slow addition of 1.0 M lithium tert-butoxide in THF solution (18 mL). The lithium tert-butoxide solution was added at such a rate that the internal temperature remained below 0° C. Fifteen minutes after the completion of base addition, the reaction (starting material gone by TLC) was quenched by adding EtOAc (65 mL) and 1.0 M hydrochloric acid (10 mL). The aqueous phase was then basified with 1N NaOH. The aqueous phase was extracted 3×EtOAc. The organics were collected together and with saturated aqueous sodium chloride solution (130 mL). The phases were separated, the organic layer was dried (MgSO4), filtered, and concentrated. Flash chromatography using a Biotage system (10% EtOAc/90% hexane to 20% EtOAc/80% Hexane) afforded the title compound in 82% yield.

1. customA clean, dry
2. customnitrogen gas purged flask
3. customremained below 0° C
4. additionFifteen minutes after the completion of base addition
5. customthe reaction (starting material gone by TLC)
6. customwas quenched
7. additionby adding EtOAc (65 mL) and 1.0 M hydrochloric acid (10 mL)
8. extractionThe aqueous phase was extracted 3×EtOAc
9. customThe organics were collected together and with saturated aqueous sodium chloride solution (130 mL)
10. customThe phases were separated
11. dry with materialthe organic layer was dried (MgSO4)
12. filtrationfiltered
13. concentrationconcentrated

ORD record

ord-8e1b62f87d064f4ca032f3815c55bcc1

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07504508B2