(Trifluoromethyl)trimethylsilane → 3-Methyl-5-[4-(2,2,2-trifluoro-1-hydroxy-ethyl)-pyridin-3-yl]-3H-benzooxazol-2-one

HRID 1253940Notes

Reaction equation

HRID 1253940 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[CH3:19][N:20]1[C:24]2[CH:25]=[C:26]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][C:34]=3[CH:35]=[O:36])[CH:27]=[CH:28][C:23]=2[O:22][C:21]1=[O:37].[F:38][C:39]([Si](C)(C)C)([F:41])[F:40]>C1COCC1.C(OCC)(=O)C.O>[CH3:19][N:20]1[C:24]2[CH:25]=[C:26]([C:29]3[CH:30]=[N:31][CH:32]=[CH:33][C:34]=3[CH:35]([OH:36])[C:39]([F:41])([F:40])[F:38])[CH:27]=[CH:28][C:23]=2[O:22][C:21]1=[O:37]

Participants

7

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium Fluoride2×HCID 866633583-(3-Methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)isonicotinaldehyde

Product 1

HCID 667978543-Methyl-5-[4-(2,2,2-trifluoro-1-hydroxy-ethyl)-pyridin-3-yl]-3H-benzooxazol-2-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of TBAF in THF (1M, 0.02 mL, 0.02 mmol) was added dropwise to a mixture of 3-(3-Methyl-2-oxo-2,3-dihydro-benzooxazol-5-yl)-pyridine-4-carbaldehyde (54 mg, 0.21 mmol) and (trifluoromethyl)trimethyl silane (0.2 mL, 0.42 mmol) in THF (0.8 mL) at 5° C. under nitrogen. After 5 min at this temperature, TBAF (1M in THF, 1 mL, 1 mmol) was added. The resulting solution was diluted with ethyl acetate and water. The organic layer was washed with brine and dried over anhydrous Na2O4. After concentration, the residue was purified by PTLC (10% MeOH in DCM, v/v) gave 3-Methyl-5-[4-(2,2,2-trifluoro-1-hydroxy-ethyl)-pyridin-3-yl]-3H-benzooxazol-2-one. (13 mg, 19%); ESI-MS m/z: 325 [M+1]+, Retention time 1.53 min; 1H-NMR (MeOD, 400 MHz) δ 8.65 (1H, d, 5.6 Hz), 8.50 (1H, s), 7.79 (1H, d, J=5.6 Hz), 7.39 (1H, d, J=8.0 Hz), 7.17 (1H d, J=1.6 Hz), 7.12 (1H, dd, J=8.0, 1.6 Hz), 5.16 (1H, q, J=6.8 Hz), 3.43 (3H, s).

Workup

  1. washThe organic layer was washed with brine
  2. customdried over anhydrous Na2O4
  3. concentrationAfter concentration
  4. customthe residue was purified by PTLC (10% MeOH in DCM, v/v)

Sources & evidence

ORD record
ord-60a71359a1a3430b8f65f71efdab9cd2
Source dataset
uspto-grants-2013_06
Patent number
US08455522B2

Reaction notes

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