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). (2) The above 4-bromo-1-fluoro-2-naphthyl-5-chloro-2-thienylmethanol was treated in a manner similar to Reference Example 1-(2) to give the desired 4-bromo-2-(5-chloro-2-thienylmethyl)-1-fluoronaphthalene as a yellow solid.

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 기록

ord-64f1386c2081499d9bfa78675e606eca

출처 데이터셋

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08202984B2