Cesium fluoride → 2-Acetyl-4-[2-(2,2-difluoroethoxy)-3,5-di-tert-butylphenyl]-benzo[b]thiophene

HRID 1394599노트

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HRID 1394599 반응식
[C:1]([C:4]1[S:8][C:7]2[CH:9]=[CH:10][CH:11]=[C:12]([C:13]3[CH:18]=[C:17]([C:19]([CH3:22])([CH3:21])[CH3:20])[CH:16]=[C:15]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:14]=3[OH:27])[C:6]=2[CH:5]=1)(=[O:3])[CH3:2].Br[CH2:29][CH:30]([F:32])[F:31].[F-].[Cs+]>CN(C=O)C>[C:1]([C:4]1[S:8][C:7]2[CH:9]=[CH:10][CH:11]=[C:12]([C:13]3[CH:18]=[C:17]([C:19]([CH3:20])([CH3:22])[CH3:21])[CH:16]=[C:15]([C:23]([CH3:26])([CH3:25])[CH3:24])[C:14]=3[O:27][CH2:29][CH:30]([F:32])[F:31])[C:6]=2[CH:5]=1)(=[O:3])[CH3:2]

참가 물질

5

반응물 3

HCID 25953Cesium fluorideHCID 1361862-Bromo-1,1-difluoroethaneHCID 596820462-Acetyl-4-(2-hydroxy-3,5-di-tert-butylphenyl)benzo[b]thiophene

생성물 1

HCID 179528082-Acetyl-4-[2-(2,2-difluoroethoxy)-3,5-di-tert-butylphenyl]-benzo[b]thiophene

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mixture of the crude 2-acetyl-4-(2-hydroxy-3,5-di-tert-butylphenyl)benzo[b]thiophene, 142.0 mg (1 mmol) of 2-bromo-1,1-difluoroethane and 410 mg (2.7 mmol) of CsF in 10 mL of dry DMF was stirred at room temperature overnight. After work-up the crude oil was filtrated over a short pad of silica gel (eluent: 10/90 ethyl acetate/hexane) to give 2-acetyl-4-[2-(2,2-difluoroethoxy)-3,5-di-tert-butylphenyl]-benzo[b]thiophene as an oil, directly used without further purification. The crude ketone was treated with the anion of triethylphosphonoacetate (previously prepared from 336 mg of triethylphosphonoacetate and 86 mg of NaH in 3 mL of dry DMF) at 60° C. After completion of the reaction (TLC monitored) and work-up, the crude ester was purified over silica gel column (eluent: 5/95 ethyl acetate/hexane) to afford 315 mg (0.65 mmol, yield: 75%, 2 steps) of pure 3-{4-[2-(2,2-difluoroethoxy)-3,5-di-tert-butylphenyl]-benzo[b]thien-2-yl}-but-2-enoic acid ethyl ester as an oil. 1H-NMR (CDCl3), δ: 7.80 (dd, J=7.2, 1.6 Hz, 1H), 7.43 (m, 4H), 7.23 (d, J=2.5 Hz, 1H), 6.29 (s, 1H), 5.17 (dt, J=55.4, 4.1 Hz, 1H), 4.21 (dd, J=14.4, 7.2 Hz, 2H), 3.50 (m, 2H), 2.57 (s, 3H), 1.47 (s, 9H), 1.34 (s, 9H), 1.31 (t, J=7.0 Hz).

후처리

  1. filtrationAfter work-up the crude oil was filtrated over a short pad of silica gel (eluent: 10/90 ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-fda788406b254e6aa7dd871188b98080
출처 데이터셋
uspto-grants-2008_03
특허 번호
US07348359B2

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