Ethyl Acetate → HCID 57389225, compound

HRID 1184733Notes

Reaction equation

HRID 1184733 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([OH:33])[CH2:15][C:16]2[C:21](Cl)=[CH:20][N:19]=[C:18]([C:23]3[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[N:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(P(C(C)(C)C)C1C=CC2C(=CC=CC=2)C=1C1C2C(=CC=CC=2)C=CC=1)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:33][C:21]3[CH:20]=[N:19][C:18]([C:23]4[CH:28]=[CH:27][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:25][CH:24]=4)=[N:17][C:16]=3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2734941(1,1'-Binaphthalen)-2-yldi-tert-butylphosphineHCID 67973476HCID 67973476, compound

Product 1

HCID 57389225HCID 57389225, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 4-{2-[5-chloro-2-(4-methanesulfonyl-phenyl)-pyrimidin-4-yl]-1-hydroxy-ethyl}-piperidine-1-carboxylic acid tert-butyl ester (50 mg), palladium acetate (3 mg), racemic 2-(di-tert-butylphosphino)-1,1′-binapthyl (6 mg), and cesium carbonate (50 mg) in toluene (1 mL) is heated in an oil bath at 70° C. under an argon atmosphere for 6 h. After cooling to room temperature ethyl acetate is added and the organic phase is separated, washed with water and brine, dried over MgSO4, and concentrated in vacuo. The residue is chromatographed on silica gel [dichloromethane/(dichloromethane/methanol/NH4OH 24:24:1) 96:4→90:10]. The crude product is triturated with diethyl ether, filtered off, and dried to give the title compound. LC (method 7): tR=1.44 min; Mass spectrum (ESI+): m/z=460 [M+H]+.

Workup

  1. additionis added
  2. customthe organic phase is separated
  3. washwashed with water and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe residue is chromatographed on silica gel [dichloromethane/(dichloromethane/methanol/NH4OH 24:24:1) 96:4→90:10]
  7. customThe crude product is triturated with diethyl ether
  8. filtrationfiltered off
  9. customdried

Sources & evidence

ORD record
ord-c05aaccbb9aa478ba44e1cc039664951
Source dataset
uspto-grants-2014_03
Patent number
US08669271B2

Reaction notes

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