Propionyl chloride → 2-Amino-4-methyl-3-oxo-butanoic acid benzyl ester hydrochloride salt

Lithium bis(trimethylsilyl)amide (1M in THF, 10.5 mL, 10.5 mmol) was added to N-(diphenylmethylene)glycine benzyl ester (3.28 g, 10 mmol) in tetrahydrofuran (10 mL) at −78° C. under argon. The reaction mixture was stirred at this temperature for about 1 hr. Propionyl chloride (0.913 mL, 10.5 mmol) in tetrahydrofuran (5 mL) was slowly added into the above mixture and stirred for 30 minutes. The reaction mixture was warmed up to room temperature and let stir overnight. After the completion of the above reaction, the reaction mixture was cooled to −40° C. quenched with 50 mL dilute hydrochloride acid (3N) and stirred at room temperature for 2 hr. After removal of tetrahydrofuran, the aqueous solution was extracted with ethyl acetate (3×50 mL), ether (1×50 mL) and CH2Cl2 (50 mL). The aqueous solution was concentrated in vacuo to about ½ volume and lyophilized to give 2-amino-4-methyl-3-oxo-butanoic acid benzyl ester hydrochloride salt, which was used in the next step without further purification.

1. stirringstirred for 30 minutes
2. stirringlet stir overnight
3. customAfter the completion of the above reaction
4. temperaturethe reaction mixture was cooled to −40° C.
5. customquenched with 50 mL dilute hydrochloride acid (3N)
6. stirringstirred at room temperature for 2 hr
7. customAfter removal of tetrahydrofuran
8. extractionthe aqueous solution was extracted with ethyl acetate (3×50 mL), ether (1×50 mL) and CH2Cl2 (50 mL)
9. concentrationThe aqueous solution was concentrated in vacuo to about ½ volume

ORD record

ord-986f484a377f4e2babc0228854c40046

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08211914B2