Acetic Acid → (S)-[2-(3,4-Dichloro-phenyl)-4-(2-oxo-[1,4']bipiperidinyl-1'-yl)-butyl]-methyl-carbamic acid tert-butyl ester

HRID 2221072Notes

Reaction equation

HRID 2221072 reaction equation
[N:1]1([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][C:2]1=[O:7].C(O)(=O)C.[C:18]([O:22][C:23](=[O:39])[N:24]([CH2:26][C@H:27]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=1)[CH2:28][CH:29]=O)[CH3:25])([CH3:21])([CH3:20])[CH3:19].[Na]>CO.C(=O)(O)[O-].[Na+]>[C:18]([O:22][C:23](=[O:39])[N:24]([CH2:26][C@H:27]([C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=1)[CH2:28][CH2:29][N:11]1[CH2:12][CH2:13][CH:8]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][C:2]2=[O:7])[CH2:9][CH2:10]1)[CH3:25])([CH3:19])([CH3:20])[CH3:21]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5360545SodiumHCID 15433413tert-Butyl [(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]methylcarbamateHCID 21839852[1,4'-Bipiperidin]-2-one

Product 1

HCID 69224867(S)-[2-(3,4-Dichloro-phenyl)-4-(2-oxo-[1,4']bipiperidinyl-1'-yl)-butyl]-methyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent3×HCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of [1,4′]bipiperidinyl-2-one (4.5 g) in methanol (100 mL) was added acetic acid (1.49 mL). The solution was stirred for several minutes before (S)-[2-(3,4-dichloro-phenyl)-4-oxo-butyl]-methyl-carbamic acid tert-butyl ester (26 mmole) was added in methanol (25 mL). Stirring was continued for 20 minutes after which time, sodium cyanoborohyuride (1.64 g) was then added in methanol (5 mL). The mixture was stirred for two days and then diluted with aqueous sodium bicarbonate and concentrated. It was then partitioned between layers of water and dichloromethane. The aqueous layers were washed with dichloromethane and the organic phases were combined, dried and evacuated to viscous oil which was purified by flash chromatography eluting with methanol:dichloromethane (5:95). This material formed a white foam upon drying under vacuum (9.4 g). MS: m/z=512(M+1).

Workup

  1. stirringThe mixture was stirred for two days
  2. concentrationconcentrated
  3. customIt was then partitioned between layers of water and dichloromethane
  4. washThe aqueous layers were washed with dichloromethane
  5. customdried
  6. customevacuated to viscous oil which
  7. customwas purified by flash chromatography
  8. washeluting with methanol:dichloromethane (5:95)
  9. customThis material formed a white foam
  10. customupon drying under vacuum (9.4 g)

Sources & evidence

ORD record
ord-fcbc2040e6eb416ba25b07fcf3798d9a
Source dataset
uspto-grants-2008_05
Patent number
US07368461B2

Reaction notes

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