2,2,6,6-Tetramethylpiperidine → 4-Bromo-1-fluoro-2-naphthyl-5-chloro-2-thienylmethanol

A solution of 2,2,6,6-tetramethylpiperidine (1.04 g) in tetrahydrofuran (15 ml) was cooled to −78° C. under argon atmosphere, and thereto was added dropwise n-butyl lithium (1.58 M hexane solution, 4.43 ml). The reaction mixture was stirred at the same temperature for 30 minutes, and thereto was added dropwise a solution of 1-bromo-4-fluoronaphthalene (1.50 g) in tetrahydrofuran (12 ml) at −78° C. The mixture was stirred at the same temperature for one hour, and thereto was added dropwise a solution of 5-chloro-2-thiophenecarboxaldehyde (1.07 g) in tetrahydrofuran (11 ml) at −78° C. The mixture was stirred at the same temperature for 30 minutes, and thereto was added a saturated aqueous ammonium chloride solution, and the reaction mixture was extracted with ethyl acetate. The extract was washed with brine, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by an aminosilane-treated silica gel column chromatography (hexane:ethyl acetate=3:1) to give 4-bromo-1-fluoro-2-naphthyl-5-chloro-2-thienylmethanol (2.00 g) as pale yellow powder. APCI-Mass m/Z 353/355 (M+H−H2O).

1. stirringThe mixture was stirred at the same temperature for one hour
2. stirringThe mixture was stirred at the same temperature for 30 minutes
3. extractionthe reaction mixture was extracted with ethyl acetate
4. washThe extract was washed with brine
5. dry with materialdried over sodium sulfate
6. customthe solvent was evaporated under reduced pressure
7. customThe residue was purified by an aminosilane-
8. additiontreated silica gel column chromatography (hexane:ethyl acetate=3:1)

ORD record

ord-9845936eb02647c69c6186b74ede8204

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08785403B2