Tetrahydrofuran → ethyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-4-oxobutanoate

HRID 1691706Notes

Reaction equation

HRID 1691706 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH:13]([CH2:14][N:15]([C@@H:23]([C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=[CH:27][CH:26]=3)[CH3:24])[C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:12][CH2:11][NH:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Cl[C:36](=[O:44])[CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40].C1COCC1.[Cl-].[NH4+]>C(N(CC)CC)C>[C:18]([O:17][C:16]([N:15]([CH2:14][CH:13]1[CH2:12][CH2:11][N:10]([C:36](=[O:44])[CH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH2:9][CH:8]1[C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=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

6

Reactant 4

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 84648Butanoic acid, 4-chloro-4-oxo-, ethyl esterHCID 59178728tert-butyl {[3-(3-fluorophenyl)piperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate

Product 1

HCID 66906545ethyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-4-oxobutanoateYield 99.7%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a mixture of 139 mg of tert-butyl {[3-(3-fluorophenyl)piperidin-4-yl]methyl}[(1R)-1-(1-naphthyl)ethyl]carbamate, 54 mg of ethyl 4-chloro-4-oxobutanoate, and 4.0 mL of THF was added 0.084 mL of triethylamine at room temperature, followed by stirring for 3 days. To the reaction mixture was added a saturated aqueous ammonium chloride solution, followed by extraction with ethyl acetate. Then, the organic layer was washed with water and saturated brine, and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to obtain 177 mg of ethyl 4-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-(3-fluorophenyl)piperidin-1-yl]-4-oxobutanoate as a colorless oily compound. ESI+: 591

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThen, the 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-0708891be5ba499c8e9abd6176478ee6
Source dataset
uspto-grants-2012_04
Patent number
US08153658B2

Reaction notes

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