Water → trans-3-(3'-Methanesulfonyl-biphenyl-3-yl)-4-phenyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 560123Notes

Reaction equation

HRID 560123 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@H:10]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22](Cl)[CH:21]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:27][S:28]([C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)(=[O:30])=[O:29].C([O-])([O-])=O.[Cs+].[Cs+].O>CC(N(C)C)=O.O>[C:6]([O-:5])(=[O:7])[CH3:27].[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@H:10]([C:20]2[CH:21]=[C:22]([C:35]3[CH:34]=[CH:33][CH:32]=[C:31]([S:28]([CH3:27])(=[O:30])=[O:29])[CH:36]=3)[CH:23]=[CH:24][CH:25]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 67001287trans-3-(3-Chloro-phenyl)-4-phenyl-piperidine-1-carboxylic acid tert-butyl ester

Product 2

HCID 175AcetateHCID 67000610trans-3-(3'-Methanesulfonyl-biphenyl-3-yl)-4-phenyl-piperidine-1-carboxylic acid tert-butyl esterYield 99.9%

Reagents, catalysts & solvents 1

HCID 21534740N,N-Dimethylacetamide--water (1/1)Solvent

Procedure

To a solution of trans-3-(3-chloro-phenyl)-4-phenyl-piperidine-1-carboxylic acid tert-butyl ester (50 mg) and 3-(methylsulfonyl)phenylboronic acid (40.3 mg) in a mixture of DMA/water (1.1 mL, 10:1) was added Cs2CO3 (87.6 mg) and [(t-Bu)2P(OH)]2PdCl2 (POPd) (8.1 mg). The reaction mixture was irradiated with microwave at 90° C. for 10 min, and at 140° C. for 10 and 15 min. Water was added, the phases were separated, and the inorganic one was extracted with ethyl acetate (×2). The organic layers were combined, washed with brine, dried (Na2SO4) and concentrated in vacuo. Column chromatography (SiO2, n-heptanelethyl acetate 1:1, and on ISOLUTE Flash NH2, n-heptane/ethyl acetate 3:1) yielded trans-3-(3′-methanesulfonyl-biphenyl-3-yl)-4-phenyl-piperidine-1-carboxylic acid tert-butyl ester (33 mg, 49%) as a colorless oil, MS: 509.3 (M+NH4)+.

Workup

  1. customThe reaction mixture was irradiated with microwave at 90° C. for 10 min
  2. customat 140° C.
  3. customfor 10 and 15 min
  4. customthe phases were separated
  5. extractionthe inorganic one was extracted with ethyl acetate (×2)
  6. washwashed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3b3dcce682b747c09f3d6655adbb1261
Source dataset
uspto-grants-2011_11
Patent number
US08063088B2

Reaction notes

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