1,1'-Carbonyldiimidazole → N-[[3,5-bis-(trifluoromethyl)phenyl]methyl]-3,4-dichloro-beta-(2-hydroxyethyl)-N-methyl-benzenepropanamide

HRID 2256322Notes

Reaction equation

HRID 2256322 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:14][C:15]([N:17]([CH2:19][C:20]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]([F:33])([F:32])[F:31])[CH:21]=2)[CH3:18])=[O:16])[CH2:10][C:11](O)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].C(N1C=CN=C1)(N1C=CN=C1)=O.[BH4-].[Na+]>CCOC(C)=O.O>[F:33][C:30]([F:31])([F:32])[C:22]1[CH:21]=[C:20]([CH2:19][N:17]([CH3:18])[C:15](=[O:16])[CH2:14][CH:9]([CH2:10][CH2:11][OH:12])[C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH:25]=[C:24]([C:26]([F:28])([F:29])[F:27])[CH:23]=1

Participants

6

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 4311764Sodium borohydrideHCID 19029324HCID 19029324, compound

Product 1

HCID 19029400N-[[3,5-bis-(trifluoromethyl)phenyl]methyl]-3,4-dichloro-beta-(2-hydroxyethyl)-N-methyl-benzenepropanamideYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

3,4-Dichloro-β[2-[[3,5-bis-(trifluoromethyl)phenylmethyl]methylamino]-2-oxoethyl]-benzenepropanoic acid (6.1 g) in EtOAc (75 mL) was treated with carbonyldiimidazole (2.43 g) and N,N-dimethylaminopyridine (150 mg). The resulting solution was stirred at room temperature for 15 minutes and then heated at 50° C. for two hours. The reaction mixture was cooled to 0° C. and treated with a solution of NaBH4 (1.8 g) in H2O (30 mL), warmed slowly to room temperature and stirred for 12 hours. The reaction mixture was diluted with EtOAc (150 mL) and washed with 1N HCl (1×100 mL), sat. NaHCO3 (1×100 mL) and water (1×100 mL). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure to yield the crude compound as a oil. Silica gel chromatography eluting with 0-10% MeOH/CH2Cl2 gave the title compound (5.7 g). Mass spectrum (FAB): 502.0791.

Workup

  1. temperatureheated at 50° C. for two hours
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. temperaturewarmed slowly to room temperature
  4. stirringstirred for 12 hours
  5. washwashed with 1N HCl (1×100 mL), sat. NaHCO3 (1×100 mL) and water (1×100 mL)
  6. dry with materialThe organic phase was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto yield the crude compound as a oil
  10. washSilica gel chromatography eluting with 0-10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-b057f8a790764a6d8fa590917b14d426
Source dataset
uspto-grants-1997_08
Patent number
US05654316

Reaction notes

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