Dimethyl Sulfoxide → 6-Fluoro-5-hydroxy-4-nitro-hexanoic acid dimethylamide

Temperature

0 °C

To a cooled (−78° C.) solution of oxalyl chloride (0.9 ml, 9.63 mmol) in anhydrous dichloromethane (5 ml) was added anhydrous DMSO (1.4 ml, 19.38 mmol) dropwise and the reaction mixture was stirred for 15 min. A solution of 2-fluoroethanol (0.44 mL, 7.5 mmol) in dichloromethane (2 ml) was slowly added into the reaction flask. The reaction mixture was stirred for 15 min, then it was diluted with dichloromethane (60 ml), followed by addition of dry Et3N (4.4 ml, 31.25 mmol). The reaction mixture was stirred for 15 min, then warmed to 0° C. and stirred at 0° C. for 2 h. To the reaction mixture was added a solution of N,N-dimethyl-4-nitro-butyramide (0.99 g, 6.25 mmol) in CH2Cl2 (5 ml). The reaction mixture was stirred at 0° C. for 3 h and then stirred at room temperature overnight. The mixture was concentrated and extracted with ethyl acetate. The organic layer were dried and evaporated. The residue was purified by silica gel (CH2Cl2/EtOAc=1:3) to give 1.23 g (89%) of the titled product as a colorless viscous oil. 1H NMR (CDCl3): 4.98 (bs, 1H), 4.81-4.72 (m, 1H), 4.70-4.61 (m, 1H), 4.59-4.37 (m, 1H), 4.33-4.18 (m, 1H), 3.02-2.98 (m, 3H), 2.94-2.93 (m, 3H), 2.46-2.22 (m, 4H).

1. stirringThe reaction mixture was stirred for 15 min
2. stirringThe reaction mixture was stirred for 15 min
3. stirringstirred at 0° C. for 2 h
4. stirringThe reaction mixture was stirred at 0° C. for 3 h
5. stirringstirred at room temperature overnight
6. concentrationThe mixture was concentrated
7. extractionextracted with ethyl acetate
8. customThe organic layer were dried
9. customevaporated
10. customThe residue was purified by silica gel (CH2Cl2/EtOAc=1:3)

ORD record

ord-0cc54313531741cf942a5ec76f15dffe

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07504382B2