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

HRID 1394599Notes

Reaction equation

HRID 1394599 reaction equation
[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]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-fda788406b254e6aa7dd871188b98080
Source dataset
uspto-grants-2008_03
Patent number
US07348359B2

Reaction notes

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