Tetrahydrofuran → 3-(methoxycarbonyl)phenyl 4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidine-1-carboxylate

HRID 1691715Notes

Reaction equation

HRID 1691715 reaction equation
[N+](C1C=CC(O[C:9]([O:11][C:12]2[CH:13]=[C:14]([CH:19]=[CH:20][CH:21]=2)[C:15]([O:17][CH3:18])=[O:16])=[O:10])=CC=1)([O-])=O.[F:24][C:25]1[CH:26]=[C:27]([CH:31]2[CH:36]([CH2:37][N:38]([C@@H:46]([C:48]3[C:57]4[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=4)[CH:51]=[CH:50][CH:49]=3)[CH3:47])[C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])[CH2:35][CH2:34][NH:33][CH2:32]2)[CH:28]=[CH:29][CH:30]=1.C1COCC1.C(=O)([O-])O.[Na+]>C(N(CC)CC)C>[C:41]([O:40][C:39]([N:38]([CH2:37][CH:36]1[CH2:35][CH2:34][N:33]([C:9]([O:11][C:12]2[CH:21]=[CH:20][CH:19]=[C:14]([C:15]([O:17][CH3:18])=[O:16])[CH:13]=2)=[O:10])[CH2:32][CH:31]1[C:27]1[CH:28]=[CH:29][CH:30]=[C:25]([F:24])[CH:26]=1)[C@@H:46]([C:48]1[C:57]2[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:51]=[CH:50][CH:49]=1)[CH3:47])=[O:45])([CH3:42])([CH3:43])[CH3:44]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 59178728tert-butyl {[3-(3-fluorophenyl)piperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamateHCID 66906106Methyl 3-{[(4-nitrophenoxy)carbonyl]oxy}benzoate

Product 1

HCID 669061673-(methoxycarbonyl)phenyl 4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidine-1-carboxylateYield 101.8%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a suspension of 5.000 g of methyl 3-hydroxybenzoate, 6.955 g of 4-nitrophenyl chloroformate, and 100 mL of toluene was added 4.81 mL of triethylamine at room temperature, followed by stirring overnight. The insolubles were removed by filtration, and as solvent was removed by distillation under reduced pressure to obtain 5.948 g of methyl 3-{[(4-nitrophenoxy)carbonyl]oxy}benzoate as a pale yellow solid. To a mixture of 100 mg of methyl 3-{[(4-nitrophenoxy)carbonyl]oxy}benzoate, 139 mg of tert-butyl {[3-(3-fluorophenyl)piperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate, and 4 ml of THF was added 0.084 mL of triethylamine at room temperature, followed by stirring overnight. A saturated aqueous sodium hydrogen carbonate solution was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 196 mg of 3-(methoxycarbonyl)phenyl 4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidine-1-carboxylate as a pale yellow oily compound.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6c3aa04bf5be425ea480b088e037cec5
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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