Ammonium Chloride → benzyl 4-fluorotetrahydro-2H-pyran-4-carboxylate

Temperature

0 °C

To a solution of the compound (0.22 g) obtained in step 1 in THF (3.5 mL) was added dropwise at −78° C. lithium bis(trimethylsilyl)amide (1.1M THF solution, 1.82 mL), and the mixture was stirred for 30 min. The mixture was warmed to 0° C. and stirred for 15 min. The reaction mixture was cooled to −78° C., a solution of N-fluoro-N-(phenylsulfonyl)benzenesulfonamide (0.63 g) in THF (2.0 mL) was added dropwise, and the mixture was stirred at −78° C. for 1 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water and saturated brine, dried and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (solvent gradient; 0→20% ethyl acetate/hexane) to give benzyl 4-fluorotetrahydro-2H-pyran-4-carboxylate (0.10 g, 44%) as a colorless oil.

1. stirringstirred for 15 min
2. temperatureThe reaction mixture was cooled to −78° C.
3. stirringthe mixture was stirred at −78° C. for 1 hr
4. extractionextracted with ethyl acetate
5. washThe extract was washed with water and saturated brine
6. customdried
7. concentrationconcentrated under reduced pressure
8. customThe residue was separated
9. custompurified by silica gel column chromatography (solvent gradient; 0→20% ethyl acetate/hexane)

ORD record

ord-d25839b1d6c74e229c79ba324f0b4af6

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592454B2