Acetone Cyanohydrin → 4-{4-[6-Chloro-2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-1-piperidinyl}tetrahydro-2H-pyran-4-carbonitrile

HRID 2064169Notes

Reaction equation

HRID 2064169 reaction equation
Cl.[F:2][C:3]([F:22])([F:21])[C:4]1[C:19]([Cl:20])=[CH:18][C:7]2[N:8]([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:9](=[O:11])[NH:10][C:6]=2[CH:5]=1.[CH3:23][C:24]([CH3:28])(O)[C:25]#[N:26].[O:29]1[CH2:34]CC(=O)C[CH2:30]1.CC(N(C)C)=O>C(OCC)(=O)C.O>[Cl:20][C:19]1[C:4]([C:3]([F:21])([F:2])[F:22])=[CH:5][C:6]2[NH:10][C:9](=[O:11])[N:8]([CH:12]3[CH2:17][CH2:16][N:15]([C:24]4([C:25]#[N:26])[CH2:28][CH2:34][O:29][CH2:30][CH2:23]4)[CH2:14][CH2:13]3)[C:7]=2[CH:18]=1

Participants

7

Reactant 4

HCID 6406Acetone CyanohydrinHCID 31374DimethylacetamideHCID 121599Tetrahydro-4H-pyran-4-oneHCID 691287645-Trifluoromethyl-6-chloro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

Product 1

HCID 598501594-{4-[6-Chloro-2-oxo-5-(trifluoromethyl)-2,3-dihydro-1H-benzimidazol-1-yl]-1-piperidinyl}tetrahydro-2H-pyran-4-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

5-Trifluoromethyl-6-chloro-1-(4-piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one hydrochloride (D64, 850 mg) was converted to the free base using SCX then combined with acetone cyanohydrin (400 mg), tetrahydropyran-4-one (500 mg) magnesium sulphate (1.5 g) and dimethylacetamide (2.5 ml), and the mixture heated under a slow stream of argon for 18 h at 60° C. To the cooled mixture were added water and ethyl acetate. The organic layer was dried over MgSO4, filtered and evaporated, and the residue was crystallised from diethyl ether to afford the subtitle compound, 160 mg.

Workup

  1. dry with materialThe organic layer was dried over MgSO4
  2. filtrationfiltered
  3. customevaporated
  4. customthe residue was crystallised from diethyl ether

Sources & evidence

ORD record
ord-80ce39c1345c44eb8a8778bdf277fddf
Source dataset
uspto-grants-2012_10
Patent number
US08288412B2

Reaction notes

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