Cesium fluoride → 1-(5-Bromothiophen-2-yl)-2,2,2-trifluoroethanol

HRID 1397378Notes

Reaction equation

HRID 1397378 reaction equation
[F-].[Cs+].[Br:3][C:4]1[S:8][C:7]([CH:9]=[O:10])=[CH:6][CH:5]=1.[F:11][C:12]([Si](C)(C)C)([F:14])[F:13]>COCCOC>[Br:3][C:4]1[S:8][C:7]([CH:9]([OH:10])[C:12]([F:14])([F:13])[F:11])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 784285-Bromothiophene-2-carbaldehydeHCID 552549(Trifluoromethyl)trimethylsilane

Product 1

HCID 199715801-(5-Bromothiophen-2-yl)-2,2,2-trifluoroethanolYield 59%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

CsF (400 mg, 2.6 mmol) was added to a solution of 5-bromothiophene-2-carbaldehyde (5.0 g, 26.17 mmol) in dry 1,2-dimethoxyethane (20 mL), followed by trifluoromethyl trimethylsilane (4.6 mL, 31.4 mmol) dropwise at 0° C. The reaction mixture was stirred at room temperature for 3 h, quenched with 1.5N HCl, and stirred for an additional 30 min. The crude product was extracted with CH2Cl2. The combined extracts were dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 5-10% EtOAc in petroleum ether) to get 1-(5-bromothiophen-2-yl)-2,2,2-trifluoroethanol (4 g, yield 59%). 1H NMR (400 MHz, CDCl3) δ 7.01 (m, 1H), 6.95 (m, 1H), 5.23-5.18 (q, J=5.9 Hz, 1H), 3.07 (br s, 1H). MS (ESI) m/z: Calculated for C6H4BrF3OS: 261.91. found: 260.7 (M−1)−.

Workup

  1. customquenched with 1.5N HCl
  2. stirringstirred for an additional 30 min
  3. extractionThe crude product was extracted with CH2Cl2
  4. dry with materialThe combined extracts were dried over anhydrous Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluant 5-10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-6a0cf7b9a853418ea10edb62b8d9ffb4
Source dataset
uspto-grants-2014_12
Patent number
US08901156B2

Reaction notes

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