4-Fluorobenzaldehyde → N-(3,5-Dichlorobenzyl)-N-(4-fluorobenzyl)-3-((4-fluorobenzylamino)methyl)benzamide

HRID 1889661Notes

Reaction equation

HRID 1889661 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:26]=[CH:27][CH:28]=1)[C:6]([N:8]([CH2:17][C:18]1[CH:23]=[C:22]([Cl:24])[CH:21]=[C:20]([Cl:25])[CH:19]=1)[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)=[O:7].[F:29][C:30]1[CH:37]=[CH:36][C:33]([CH:34]=O)=[CH:32][CH:31]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CC(O)C>[Cl:25][C:20]1[CH:19]=[C:18]([CH:23]=[C:22]([Cl:24])[CH:21]=1)[CH2:17][N:8]([CH2:9][C:10]1[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=1)[C:6](=[O:7])[C:5]1[CH:26]=[CH:27][CH:28]=[C:3]([CH2:2][NH:1][CH2:34][C:33]2[CH:36]=[CH:37][C:30]([F:29])=[CH:31][CH:32]=2)[CH:4]=1

Participants

7

Reactant 4

HCID 680234-FluorobenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 585314683-(Aminomethyl)-N-(3,5-dichlorobenzyl)-N-(4-fluorobenzyl)benzamide

Product 1

HCID 58531676N-(3,5-Dichlorobenzyl)-N-(4-fluorobenzyl)-3-((4-fluorobenzylamino)methyl)benzamideYield 63%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-(aminomethyl)-N-(3,5-dichlorobenzyl)-N-(4-fluorobenzyl)benzamide (0.6 g, 1.44 mmol) in CH2Cl2 (6.0 mL) and 2-propanol (6.0 mL) was added 4-fluorobenzaldehyde (0.16 mL, 1.44 mmol). The resulting mixture was stirred at rt for 1.5 h. The reaction mixture was cooled to ice bath temperature and was added sodium triacetoxyborohydride (0.49 g, 2.30 mmol) under N2 atmosphere. The resulting mixture was stirred at rt for 20 h. To the reaction mixture was added saturated aq NaHCO3 solution and the mixture was stirred for 20 minutes. The mixture was concentrated, and the residue was diluted with ethyl acetate and saturated aq NaHCO3 solution. The organic layer was separated, washed with brine, dried over MgSO4 and concentrated. The residue was purified by flash chromatography on silica gel (ISCO. condition: 24 g column; eluents: 0-25% of ethyl acetate in CH2Cl2, gradient over 40 minutes) to obtain the desired product as colorless oil (0.47, 63%). 1H NMR (CDCl3): δ 7.55-7.29 (m, 7H), 7.17-7.00 (m, 8H), 4.70-4.63 (m, 2H), 4.43-4.36 (m, 2H), 3.82 (s, 2H), 3.77 (s, 2H); MS (ESI): [M+H]+=524.9.

Workup

  1. temperatureThe reaction mixture was cooled to ice bath temperature
  2. stirringThe resulting mixture was stirred at rt for 20 h
  3. stirringthe mixture was stirred for 20 minutes
  4. concentrationThe mixture was concentrated
  5. additionthe residue was diluted with ethyl acetate and saturated aq NaHCO3 solution
  6. customThe organic layer was separated
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel (ISCO. condition: 24 g column; eluents: 0-25% of ethyl acetate in CH2Cl2, gradient over 40 minutes)

Sources & evidence

ORD record
ord-43d62a1dc70e479ea24a10e58d527d65
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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