Potassium tert-butoxide → 4-(5-Trifluoromethyl-benzo[d]isoxazol-3-yl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 501314Notes

Reaction equation

HRID 501314 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=2F)=[N:15][OH:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:17]3[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[CH:19][C:18]=3[O:16][N:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 23665647Potassium tert-butoxideHCID 724345474-[(2-Fluoro-5-trifluoromethyl-phenyl)-hydroxyiminomethyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 588175304-(5-Trifluoromethyl-benzo[d]isoxazol-3-yl)-piperidine-1-carboxylic acid tert-butyl esterYield 106.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 4-[(2-Fluoro-5-trifluoromethyl-phenyl)-hydroxyimino-methyl]-piperidine-1-carboxylic acid tert-butyl ester (4.969 g, 0.013 M) in anhydrous THF (59 mL) was treated with Potassium tert-butoxide (13.4 mL of a 1M solution in THF, 0.0133 M-1.05 eq). The mixture was stirred at ambient temperature for 1 hour and then heated to 65° C. for 2 hours. The THF was removed under reduced pressure. The residue was dissolved in ethyl acetate (100 mL), washed with H2O (50 mL) and brine (50 mL) respectively. It was then dried over MgSO4, filtered and concentrated to give a solid (5 g) which was purified on silica ˜120 g, (eluting with ethylacetate heptane (30:70) to give the product as a white solid (2.69 g, 57%).

Workup

  1. temperatureheated to 65° C. for 2 hours
  2. customThe THF was removed under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  4. washwashed with H2O (50 mL) and brine (50 mL) respectively
  5. dry with materialIt was then dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-cc987dde104b489ab6857cf32d915e8a
Source dataset
uspto-grants-2010_08
Patent number
US07772252B2

Reaction notes

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