Sodium Methoxide → 1,1,1-Trifluoro-2-(4-(4-(1-tosylpiperidin-4-yl)oxazol-5-yl)phenyl)propan-2-ol

HRID 1616344Notes

Reaction equation

HRID 1616344 reaction equation
[N+:1]([CH:3](S(C1C=CC(C)=CC=1)(=O)=O)[CH:4]1[CH2:9][CH2:8][N:7]([S:10]([C:13]2[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[CH2:6][CH2:5]1)#[C-:2].C[O-].[Na+].[F:33][C:34]([F:47])([F:46])[C:35]([C:38]1[CH:45]=[CH:44][C:41]([CH:42]=[O:43])=[CH:40][CH:39]=1)([OH:37])[CH3:36]>CO.C(OCC)(=O)C.C([O-])(O)=O.[Na+]>[F:33][C:34]([F:46])([F:47])[C:35]([C:38]1[CH:45]=[CH:44][C:41]([C:42]2[O:43][CH:2]=[N:1][C:3]=2[CH:4]2[CH2:5][CH2:6][N:7]([S:10]([C:13]3[CH:19]=[CH:18][C:16]([CH3:17])=[CH:15][CH:14]=3)(=[O:11])=[O:12])[CH2:8][CH2:9]2)=[CH:40][CH:39]=1)([OH:37])[CH3:36]

Participants

7

Reactant 3

HCID 10942334Sodium MethoxideHCID 595655894-(Isocyano(tosyl)methyl)-1-tosylpiperidineHCID 595655994-(1,1,1-Trifluoro-2-hydroxypropan-2-yl)benzaldehyde

Product 1

HCID 252039711,1,1-Trifluoro-2-(4-(4-(1-tosylpiperidin-4-yl)oxazol-5-yl)phenyl)propan-2-ol

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

4-(Isocyano(tosyl)methyl)-1-tosylpiperidine (260 mg, 0.73 mmol) was dissolved in MeOH (6 mL) and treated with sodium methoxide (1.0 M solution in MeOH, 0.7 mL), and 4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzaldehyde (159 mg, 0.73 mmol) was then added. After being stirred at 80° C. for 2 h, the mixture was then cooled to r.t. and diluted with ethyl acetate (80 mL) and saturated aqueous NaHCO3 (30 mL). The separated organic layer was dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (15% EtOAc/hexane) to provide 1,1,1-trifluoro-2-(4-(4-(1-tosylpiperidin-4-yl)oxazol-5-yl)phenyl)propan-2-ol as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.83 (s, 1H), 7.69-7.65 (m, 2H), 7.51-7.49 (m, 2H), 7.36-7.33 (m, 4H), 3.90 (d, J=11.7 Hz, 2H), 3.30-3.28 (s, 1H), 2.79 (tt, J=3.9 Hz, 11.7 Hz, 1H), 2.45 (s, 3H), 2.37 (td, J=2.3 Hz, 12.1 Hz, 2H), 2.17-2.07 (m, 2H), 1.85 (d, J=12.1 Hz, 2H), 1.80 (s, 3H); MS (ESI) 495.1 (M+H)+.

Workup

  1. additionwas then added
  2. temperaturethe mixture was then cooled to r.t.
  3. dry with materialThe separated organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (15% EtOAc/hexane)

Sources & evidence

ORD record
ord-40687ac5d5604f9c9db46fb4ee435620
Source dataset
uspto-grants-2014_07
Patent number
US08765788B2

Reaction notes

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