Diisopropylamine → tert-Butyl 5-chloro-3-oxopentanoate

To a stirred solution of diisoproply amine (20 mmol, 2.02 g, 3.05 ml) in dry THF (20 ml) at -78° C. was added n-butyllithium (20 mmol), 7.7 ml; 2.6M solution in hexanes. After stirring for 30 minutes, t-butyl acetate (22 mmol, 2.56 g) was added dropwise and the resulting mixture was stirred for 15 minutes. A solution of the lithium enolate of t-butyl acetate was subsequently added by cannula to a solution of ethyl 3-chloropropanoate (10 mmol, 1.37 g) in THF (25 ml) at -78° C. over 15 minutes. After stirring for an additional 15 minutes, the reaction was quenched by addition of glacial acetic acid (10 ml). After heating to room temperature, the reaction mixture was diluted with water (50 ml) and extracted with ether (150 ml). The ethereal extract was washed with 20% aqueous K2CO3 (2×100 ml), the organic phase was dried (MgSO4) and then concentrated in vacuo. Purification of the resulting liquid by gradient flash chromatography (SiO2, 1) 5% Et2O/pentane, 2) 15% Et2O/pentane) afforded t-butyl 5-chloro-3-oxopentanoate as a clear, colorless oil (4.08 g, 99%).

1. stirringthe resulting mixture was stirred for 15 minutes
2. stirringAfter stirring for an additional 15 minutes
3. customthe reaction was quenched by addition of glacial acetic acid (10 ml)
4. additionthe reaction mixture was diluted with water (50 ml)
5. extractionextracted with ether (150 ml)
6. extractionThe ethereal extract
7. washwas washed with 20% aqueous K2CO3 (2×100 ml)
8. dry with materialthe organic phase was dried (MgSO4)
9. concentrationconcentrated in vacuo
10. customPurification of the resulting liquid by gradient flash chromatography (SiO2, 1) 5% Et2O/pentane, 2) 15% Et2O/pentane)

ORD record

ord-2b8e6ec981b8420ea40928702d78dc71

Source dataset

uspto-grants-1990_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04929751