Benzaldehyde → (RS)-N-(3,5-Bis-trifluoromethyl-benzyl)-6-(hydroxy-phenyl-methyl)-N-methyl-4-o-tolyl-nicotinamide

HRID 1835356Notes

Reaction equation

HRID 1835356 reaction equation
C([Mg]Br)(C)C.[F:6][C:7]([F:38])([F:37])[C:8]1[CH:9]=[C:10]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:11][N:12]([CH3:29])[C:13](=[O:28])[C:14]1[C:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])=[CH:18][C:17](I)=[N:16][CH:15]=1.[CH:39](=[O:46])[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.[Cl-].[NH4+]>O1CCCC1.O>[F:6][C:7]([F:38])([F:37])[C:8]1[CH:9]=[C:10]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:11][N:12]([CH3:29])[C:13](=[O:28])[C:14]1[C:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[CH3:26])=[CH:18][C:17]([CH:39]([OH:46])[C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[N:16][CH:15]=1

Participants

7

Reactant 4

HCID 240BenzaldehydeHCID 25517Ammonium ChlorideHCID 10231844N-(3,5-Bis-trifluoromethyl-benzyl)-6-iodo-N-methyl-4-o-tolyl-nicotinamideHCID 178418365HCID 178418365, compound

Product 1

HCID 23502874(RS)-N-(3,5-Bis-trifluoromethyl-benzyl)-6-(hydroxy-phenyl-methyl)-N-methyl-4-o-tolyl-nicotinamideYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To 1.8 ml of a 1 M solution of isopropyl magnesium bromide in tetrahydrofuran (1.8 mmol) a solution of 500 mg (0.865 mmol) N-(3,5-bis-trifluoromethyl-benzyl)-6-iodo-N-methyl-4-o-tolyl-nicotinamide (Example 4) in 10 ml tetrahydrofuran was added dropwise at 40° C. After 2 h 0.116 ml (I1.15 mmol) benzaldehyde were added. The reaction mixture was allowed to warm to room temperature over night. Addition of water and saturated aqueous ammonium chloride solution was followed by extraction with three portions of ethyl acetate. The combined organic extracts were dried with sodium sulfate and concentrated. Column chromatography afforded 274 mg (57%) of the title compound as an off-white foam.

Workup

  1. extractionwas followed by extraction with three portions of ethyl acetate
  2. dry with materialThe combined organic extracts were dried with sodium sulfate
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-46c116e5a6e346289d6609693c5941cd
Source dataset
uspto-grants-2004_08
Patent number
US06770637B2

Reaction notes

Loading…