반응 #308306

반응 방정식

5-chloro-2-thiophenecarboxaldehyde

2,2,6,6-tetramethylpiperidine

n-butyl lithium

ammonium chloride

1-bromo-4-fluoronaphthalene

→

4-bromo-1-fluoro-2-naphthyl-5-chloro-2-thienylmethanol

수율 80.7%

용매

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.STIRRINGThe mixture was stirred at the same temperature for one hour
2. 2
   workup.STIRRINGThe mixture was stirred at the same temperature for 30 minutes
3. 3
   추출the reaction mixture was extracted with ethyl acetate
4. 4
   세척The extract was washed with brine
5. 5
   건조dried over sodium sulfate
6. 6
   기타the solvent was evaporated under reduced pressure
7. 7
   기타The residue was purified by an aminosilane-
8. 8
   workup.ADDITIONtreated silica gel column chromatography (hexane:ethyl acetate=3:1)

실험 절차

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.

출처