Acetyl chloride → Ethyl 2-amino-3-oxobutanoate hydrochloride

Ethyl 2-amino-3-oxobutanoate hydrochloride was prepared as described in J. Med. Chem. 1996, 39, 957. LiHMDS (50 mL, 50 mmol, 1 M in THF) was slowly added to a solution of ethyl N-(diphenylmethylidene)glycinate in THF (62.5 mL) at −78° C. under N2. The yellow slurry was stirred for 45 min. and was then transferred via cannula to a solution of acetyl chloride (4.2 mL, 59 mmol) in THF (25 mL) at −78° C. Additional THF (125 mL) was added to the anion solution to facilitate transfer to the acetyl chloride solution. The reaction mixture was allowed to warm to RT and stirred for 4 h. The reaction was then quenched with 2 N HCl (57.5 mL). The THF was evaporated and the resultant aqueous solution was extracted with EtOAc (2×50 mL). The organic phases were discarded and the aqueous phase was concentrated in vacuo. The residue was treated with EtOH (75 mL) and filtered. The filtrate was concentrated in vacuo to give the title compound (9.6 g, >99%) as a light-yellow solid which was used in next step without purification.

1. customEthyl 2-amino-3-oxobutanoate hydrochloride was prepared
2. stirringstirred for 4 h
3. customThe reaction was then quenched with 2 N HCl (57.5 mL)
4. customThe THF was evaporated
5. extractionthe resultant aqueous solution was extracted with EtOAc (2×50 mL)
6. concentrationthe aqueous phase was concentrated in vacuo
7. additionThe residue was treated with EtOH (75 mL)
8. filtrationfiltered
9. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-1a107089a7424bf8b05fc59189091b9a

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304419B2