Tetrahydrofuran → HCID 66906070, compound

HRID 1691759Notes

Reaction equation

HRID 1691759 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH:9]1[CH2:14][N:15]([C@@H:23]([C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1)[CH3:24])[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19].[F:35][C:36]1[CH:37]=[C:38]([CH:43]=[C:44]([F:47])[C:45]=1F)[C:39]([O:41][CH3:42])=[O:40].C(=O)([O-])[O-].[K+].[K+].C1COCC1>O.CS(C)=O>[C:18]([O:17][C:16]([N:15]([CH2:14][C@@H:9]1[C@@H:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[F:1])[CH2:13][CH2:12][N:11]([C:45]2[C:44]([F:47])=[CH:43][C:38]([C:39]([O:41][CH3:42])=[O:40])=[CH:37][C:36]=2[F:35])[CH2:10]1)[C@@H:23]([C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=2)[CH:28]=[CH:27][CH:26]=1)[CH3:24])=[O:22])([CH3:19])([CH3:21])[CH3:20]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 2783211Methyl 3,4,5-trifluorobenzoateHCID 59178528HCID 59178528, compound

Product 1

HCID 66906070HCID 66906070, compoundYield 56.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 191 mg of tert-butyl {[4-(2-fluorophenyl)piperidin-3-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate, 118 mg of methyl 3,4,5-trifluorobenzoate, 114 mg of potassium carbonate, and 2.0 mL of THF-2.0 mL of DMSO was stirred at 100° C. overnight. After cooling, to the reaction mixture was added water, followed by extraction with ethyl acetate, and then drying over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 147 mg of methyl 4-[(3R,4S)-3-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-4-(2-fluorophenyl)piperidin-1-yl]-3,5-difluorobenzoate as a colorless amorphous substance.

Workup

  1. temperatureAfter cooling, to the reaction mixture
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialdrying over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-c0b7a3222eb7452289e147680bc383d1
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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