3,5-Difluorobenzaldehyde → 2-{5-[1-(3,5-Difluoro-benzyl)-piperidin-4-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester

HRID 889758Notes

Reaction equation

HRID 889758 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[CH:5]([C:10]1[CH:11]=[C:12]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=2)[CH:13]=[C:14]([CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2].[F:33][C:34]1[CH:35]=[C:36]([CH:39]=[C:40]([F:42])[CH:41]=1)[CH:37]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([O:3][C:4](=[O:32])[CH:5]([C:10]1[CH:11]=[C:12]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([F:29])([F:30])[F:31])=[CH:24][CH:23]=2)[CH:13]=[C:14]([CH:16]2[CH2:17][CH2:18][N:19]([CH2:37][C:36]3[CH:35]=[C:34]([F:33])[CH:41]=[C:40]([F:42])[CH:39]=3)[CH2:20][CH2:21]2)[CH:15]=1)[CH2:6][CH:7]([CH3:9])[CH3:8])[CH3:2]

Participants

5

Reactant 3

HCID 5881603,5-DifluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 576660434-Methyl-2-(5-piperidin-4-yl-4'-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester

Product 1

HCID 576660002-{5-[1-(3,5-Difluoro-benzyl)-piperidin-4-yl]-4'-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of a mixture of 4-methyl-2-(5-piperidin-4-yl-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester and methyl ester (68b) (50 mg, 0.11 mmol) in 1,2-dichloroethane (1.0 mL) was added 3,5-difluorobenzaldehyde (0.014 mL, 0.12 mmol) and sodiumtriacetoxyborohydride (31 mg, 0.14 mmol). The mixture was stirred for 2 h at room temperature. The reaction was quenched with water and extracted with dichloromethane. The organic was washed with saturated aqueous NaHCO3 solution and brine. The organic fraction was dried (MgSO4) and concentrated in vacuo. The crude mixture contained 2-{5-[1-(3,5-difluoro-benzyl)-piperidin-4-yl]-4′-trifluoromethyl-biphenyl-3-yl}-4-methyl-pentanoic acid ethyl ester and methyl ester. Calcd for C32H34F5NO2 (M+H) 560.61, Found 560.3 (methyl ester) and Calcd for C33H36F5NO2 (M+H) 574.64, Found 574.2 (ethyl ester).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with dichloromethane
  3. washThe organic was washed with saturated aqueous NaHCO3 solution and brine
  4. dry with materialThe organic fraction was dried (MgSO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7b7b9b99ea51439dbb5a9a383c129e7c
Source dataset
uspto-grants-2012_08
Patent number
US08252935B2

Reaction notes

Loading…