Ethyl Acetate → N-[4-(2-Chloro-phenyl)-pyridin-3-yl]-N-(2-hydroxy-ethyl)-3,5-bis-trifluoromethyl-benzamide

HRID 878115Notes

Reaction equation

HRID 878115 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[N:14]([CH2:31][C:32](OC)=[O:33])[C:15](=[O:30])[C:16]1[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=1.[BH4-].[Na+].[NH4+].[Cl-].CCOC(C)=O>CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[N:14]([CH2:31][CH2:32][OH:33])[C:15](=[O:30])[C:16]1[CH:17]=[C:18]([C:26]([F:28])([F:29])[F:27])[CH:19]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:21]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 86670721HCID 86670721, compound

Product 1

HCID 86670736N-[4-(2-Chloro-phenyl)-pyridin-3-yl]-N-(2-hydroxy-ethyl)-3,5-bis-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The solution of methyl 2-(N-(4-(2-chlorophenyl)pyridin-3-yl)-3,5-bis(trifluoromethyl)benzamido)acetate (0.15 g, 0.29 mmol, example 88) in methanol (2.00 mL) was cooled down to 0° C. To the light yellow suspension was added NaBH4 (22.0 mg, 0.58 mmol) and the reaction was stirred for 2 h at room temperature. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were washed with brine, dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 30:70). The product containing fractions were combined and partially evaporated upon which crystallisation started. The supernatant light brown solution was pipetted off and the remaining solid dried under high vacuum. Colorless crystals (0.024 g; 16%). MS (ESI): m/z=489.08 [M+H]+.

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted twice with EtOAc
  3. washThe organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. additiontreated with silica gel
  7. customevaporated
  8. customThe compound was purified by silica gel chromatography on a 10 g column
  9. washeluting with a gradient of n-heptane:EtOAc (100:0 to 30:70)
  10. additionThe product containing fractions
  11. custompartially evaporated upon which crystallisation
  12. customthe remaining solid dried under high vacuum

Sources & evidence

ORD record
ord-a7b7acdfe753408a91fdf277aba06235
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

Loading…