Water ethylacetate → (Rs)-2-[2-(1-{1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanoyl}-piperidin-2-ylmethyl)-3h-imidazol-4-yl]-benzonitrile

HRID 30192Notes

Reaction equation

HRID 30192 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[N:10][C:9]=2[C:14]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]2[CH2:22][C:23]2[NH:24][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3Br)=[CH:26][N:27]=2)=[O:15])=[CH:4][CH:3]=1.[Cu][C:36]#[N:37].C(OCC)(=O)C.O>CN1CCCC1=O.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH3:13])=[N:10][C:9]=2[C:14]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH:17]2[CH2:22][C:23]2[NH:24][C:25]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:36]#[N:37])=[CH:26][N:27]=2)=[O:15])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 22728543Water ethylacetateHCID 67157688HCID 67157688, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 67157921(Rs)-2-[2-(1-{1-[5-(4-fluoro-phenyl)-2-methyl-thiazol-4-yl]-methanoyl}-piperidin-2-ylmethyl)-3h-imidazol-4-yl]-benzonitrileYield 30.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

The compound of example 95 (0.11 g) and copper(I) cyanide (0.03 g) were combined in N-methylpyrrolidinone (5 ml) and the mixture boiled for 6 h. After cooling to room temperature the reaction mixture was stood overnight, diluted with ethyl acetate, passed through silica gel eluting with ethyl acetate/water. The organic phase was separated washed with water dried (MgSO4) and solvent removed at reduced pressure. The residue was column chromatographed (silica gel, 20→100% ethyl acetate/pentane), the appropriate fractions combined and solvent removed at reduced pressure to give the title compound (0.03 g) as a gum

Workup

  1. waitwas stood overnight
  2. customThe organic phase was separated
  3. washwashed with water
  4. dry with materialdried (MgSO4) and solvent
  5. customremoved at reduced pressure
  6. customchromatographed (silica gel, 20→100% ethyl acetate/pentane)
  7. customsolvent removed at reduced pressure

Sources & evidence

ORD record
ord-595b4e2fa28f40eca84ebe34ac0b5276
Source dataset
uspto-grants-2008_09
Patent number
US07423052B2

Reaction notes

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