Acetic Acid → N-(3-{1-[4-(3,4-Difluorophenoxy)benzyl]-4-piperidinyl}-4-methylphenyl)-2-methylpropanamide

HRID 1832266Notes

Reaction equation

HRID 1832266 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[F:17])[O:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=O)=[CH:8][CH:7]=1.[CH3:18][CH:19]([CH3:36])[C:20]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[C:25]([CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:24]=1)=[O:21].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>ClCCCl>[F:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[F:17])[O:5][C:6]1[CH:13]=[CH:12][C:9]([CH2:10][N:33]2[CH2:34][CH2:35][CH:30]([C:25]3[CH:24]=[C:23]([NH:22][C:20](=[O:21])[CH:19]([CH3:18])[CH3:36])[CH:28]=[CH:27][C:26]=3[CH3:29])[CH2:31][CH2:32]2)=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 105857414-(3,4-Difluorophenoxy)benzaldehydeHCID 167572542-Methyl-N-[4-methyl-3-(4-piperidinyl)phenyl]propanamide

Product 1

HCID 16756754N-(3-{1-[4-(3,4-Difluorophenoxy)benzyl]-4-piperidinyl}-4-methylphenyl)-2-methylpropanamideYield 54.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 4-(3,4-Difluorophenoxy)benzaldehyde (41.0 mg, 0.170 mmol) and 2-methyl-N-[4-methyl-3-(4-piperidinyl)phenyl]propanamide (45.0 mg, 0.170 mmol) in 1,2-dichloroethane (5.00 mL) was added sodium triacetoxyborohydride (110 mg, 0.520 mmol) and AcOH (10.0 μL, 0.170 mmol) at room temperature. The mixture was stirred overnight. The reaction mixture was quenched by saturated NaHCO3 solution (10 mL) and extracted with CH2Cl2 (3×10 mL). The combined organic layers were washed with brine, dried over MgSO4, concentrated in vacuo. The crude product was purified by preparative TLC using 5% NH3 {2.0 M in MeOH) in CH2Cl2 to give the desired product N-(3-{1-[4-(3,4-difluorophenoxy)benzyl]-4-piperidinyl}-4-methylphenyl)-2-methylpropanamide (44.0 mg, 54.0%).

Workup

  1. customThe reaction mixture was quenched by saturated NaHCO3 solution (10 mL)
  2. extractionextracted with CH2Cl2 (3×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-6e047296718c40bc8b365e0a098b2b31
Source dataset
uspto-grants-2006_06
Patent number
US07067534B1

Reaction notes

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