Cesium fluoride → Methyl 4-(5-(2,2,2-trifluoro-1-hydroxyethyl)thiophen-2-yl)butanoate

HRID 874989Notes

Reaction equation

HRID 874989 reaction equation
[F-].[Cs+].[CH:3]([C:5]1[S:9][C:8]([CH2:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:6]=1)=[O:4].[F:17][C:18]([Si](C)(C)C)([F:20])[F:19]>COCCOC>[F:17][C:18]([F:20])([F:19])[CH:3]([C:5]1[S:9][C:8]([CH2:10][CH2:11][CH2:12][C:13]([O:15][CH3:16])=[O:14])=[CH:7][CH:6]=1)[OH:4]

Participants

5

Reactant 3

HCID 25953Cesium fluorideHCID 552549(Trifluoromethyl)trimethylsilaneHCID 53861603Methyl 4-(5-formylthiophen-2-yl)butanoate

Product 1

HCID 67322971Methyl 4-(5-(2,2,2-trifluoro-1-hydroxyethyl)thiophen-2-yl)butanoateYield 47.4%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

CsF (70 mg, 0.47 mmol) was added to a solution of methyl 4-(5-formylthiophen-2-yl)butanoate (1.0 g, 4.71 mmol) in dry 1,2-dimethoxyethane (5 MI) at 0° C., followed by trifluoromethyl trimethylsilane (0.8 MI, 5.65 mmol) dropwise. The reaction mixture was stirred at room temperature for 4 h, quenched with 3N HCl, and stirred for further 30 min. The crude product was extracted with EtOAc. The combined extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 10% EtOAc in petroleum ether) to get methyl 4-(5-(2,2,2-trifluoro-1-hydroxyethyl)thiophen-2-yl)butanoate (0.63 g, yield 47%) as yellow liquid. 1H NMR (400 MHz, CDCl3) δ 7.02-7.01 (d, J=3.5 Hz, 1H), 6.74-6.73 (m, 1H), 5.23-5.17 (m, 1H), 3.68 (s, 3H), 2.88-2.84 (t, J=7.5 Hz, 2H), 2.81-2.80 (d, J=5.3 Hz, 1H), 2.40-2.36 (t, J=7.5 Hz, 2H), 2.05-1.97 (m, 2H).

Workup

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

Sources & evidence

ORD record
ord-52e837c09de94d048e031f9983f22e18
Source dataset
uspto-grants-2015_03
Patent number
US08981084B2

Reaction notes

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