3-Fluorobenzaldehyde → 2-[(3-fluorophenyl)(hydroxy)methyl]-4-methoxy-N-methylbenzamide

HRID 2196385Notes

Reaction equation

HRID 2196385 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:6]([C:7]([NH:9][CH3:10])=[O:8])=[CH:5][CH:4]=1.[Li]CCCC.[F:18][C:19]1[CH:20]=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=[O:23]>C1COCC1>[F:18][C:19]1[CH:20]=[C:21]([CH:22]([OH:23])[C:11]2[CH:12]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=2[C:7]([NH:9][CH3:10])=[O:8])[CH:24]=[CH:25][CH:26]=1

Participants

5

Reactant 3

HCID 680093-FluorobenzaldehydeHCID 3460314-methoxy-N-methylbenzamideHCID 178418339Butyllithium

Product 1

HCID 685140052-[(3-fluorophenyl)(hydroxy)methyl]-4-methoxy-N-methylbenzamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a −78 C solution of 4-methoxy-N-methylbenzamide (2.0 g) in THF was added n-BuLi (10 mL, 2.5 M in hexanes). The reaction was stirred for 10 min at −78 C, warmed to 0 C, then cooled back to −78 C. 3-fluorobenzaldehyde (1.90 mL) was added as a solution in THF via cannula. The reaction was warmed to room temp, then quenched with saturated aqueous NH4Cl. The mixture was extracted with EtOAc, concentrated, and purified by flash chromatography (5% MeOH in CH2Cl2) to give 2-[(3-fluorophenyl) (hydroxy)methyl]-4-methoxy-N-methylbenzamide.

Workup

  1. temperaturewarmed to 0 C
  2. temperaturecooled back to −78 C
  3. customquenched with saturated aqueous NH4Cl
  4. extractionThe mixture was extracted with EtOAc
  5. concentrationconcentrated
  6. custompurified by flash chromatography (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-55dcba5398b54fcaafb57ab57cf1f501
Source dataset
uspto-grants-2012_12
Patent number
US08338449B2

Reaction notes

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