Water → 1,1-Dimethylethyl [(4r)-4-(5-chloro-2-cyano-4-fluorophenoxy)-4-(1-methyl-1h-imidazol-2-yl)butyl]-carbamate

HRID 352132Notes

Reaction equation

HRID 352132 reaction equation
[CH3:1][C:2]([O:5][C:6](=[O:19])[NH:7][CH2:8][CH2:9][CH2:10][C@@H:11]([OH:18])[C:12]1[N:13]([CH3:17])[CH:14]=[CH:15][N:16]=1)([CH3:4])[CH3:3].[H-].[Na+].[Cl:22][C:23]1[C:30]([F:31])=[CH:29][C:26]([C:27]#[N:28])=[C:25](F)[CH:24]=1.O>CN(C)C=O>[Cl:22][C:23]1[C:30]([F:31])=[CH:29][C:26]([C:27]#[N:28])=[C:25]([CH:24]=1)[O:18][C@@H:11]([C:12]1[N:13]([CH3:17])[CH:14]=[CH:15][N:16]=1)[CH2:10][CH2:9][CH2:8][NH:7][C:6](=[O:19])[O:5][C:2]([CH3:1])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 112753024-Chloro-2,5-difluorobenzonitrileHCID 131724444[(4R)-4-Hydroxy-4-(1-methyl-1H-imidazol-2-yl)butyl]carbamic acid 1,1-dimethylethyl ester

Product 1

HCID 914130451,1-Dimethylethyl [(4r)-4-(5-chloro-2-cyano-4-fluorophenoxy)-4-(1-methyl-1h-imidazol-2-yl)butyl]-carbamateYield 89.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

The product of step (b) (0.24 g, 0.9 mmol) was dissolved in dry dimethylformamide (20 ml), sodium hydride (60% dispersion in oil, 0.04 g, 0.95 mmol) was added in one portion and the mixture stirred at room temperature for 0.5 h. 4-Chloro-2,5-difluorobenzonitrile (0.16 g, 0.9 mmol), as a solution in dry dimethylformamide (5 ml), was added dropwise and the reaction stirred for 18hat room temperature. Water (25 ml) was added and the reaction mixture extracted with ethyl acetate (3×60 ml). The combined organic extracts were washed with water (2×20 ml), dried (magnesium sulphate) and evaporated. The residue was eluted down a flash chromatography column using hexane:ethyl acetate (1:3) as eluent to give the sub-title compound as a white crystalline solid (0.34 g, 88%).

Workup

  1. stirringthe reaction stirred for 18hat room temperature
  2. extractionthe reaction mixture extracted with ethyl acetate (3×60 ml)
  3. washThe combined organic extracts were washed with water (2×20 ml)
  4. dry with materialdried (magnesium sulphate)
  5. customevaporated
  6. washThe residue was eluted down a flash chromatography column

Sources & evidence

ORD record
ord-45c373d6c6844181bfd1b0354ab65a95
Source dataset
uspto-grants-2004_06
Patent number
US06743939B2

Reaction notes

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