Dimethyl Sulfoxide → t-Butyl 5-fluoro-4-hydroxy-3-nitropentanoate

A solution of oxalyl chloride (1.9 mL, 21.8 mmol) in dry CH2Cl2 (100 mL) was cooled to −78° C., a solution of DMSO (3.0 mL, 42.3 mmol) in dry CH2Cl2 (10 mL) was added with stirring in such a rate that the temperature was kept at −50 to −60° C. After 5 min stirring, a solution of 2-fluoroethanol (1.2 mL, 18.4 mmol) in dry CH2Cl2 (10 mL) was added, and stirring was continued for an additional 15 min, then dry Et3N (13.5 mL) was added. The reaction mixture was stirred for 15 min, then allowed to warm to rt. To the reaction mixture was added a solution of t-butyl 3-nitropropionate (2.87 g, 16.38 mmol) in CH2Cl2 (20 mL). The reaction mixture was stirred at rt for 3 h, then poured into water (100 mL). The organic layer was separated and the aqueous was extracted with CH2Cl2 (2×50 mL). The CH2Cl2 solution was washed with brine, dried and evaporated. The residue was purified by chromatography twice over silica gel (hexane-EtOAc, 7:3) to give 950 mg (24.5%) of the titled product as a colorless viscous oil. 1H NMR (CDCl3), 1.450 (s, 9H), 2.80-2.90 (m, 2H), 3.12-3.20 (m, 1H), 4.41-4.59 (m, 2H), 4.57-4.59 (m, 1H), 4.95-5.01 (m, 1H).

1. customwas kept at −50 to −60° C
2. stirringAfter 5 min stirring
3. stirringstirring
4. stirringThe reaction mixture was stirred for 15 min
5. stirringThe reaction mixture was stirred at rt for 3 h
6. customThe organic layer was separated
7. extractionthe aqueous was extracted with CH2Cl2 (2×50 mL)
8. washThe CH2Cl2 solution was washed with brine
9. customdried
10. customevaporated
11. customThe residue was purified by chromatography twice over silica gel (hexane-EtOAc, 7:3)

ORD record

ord-862a3c660a69476693dc86b1b74e2f36

Source dataset

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06184210B2