Sodium hydride → 2-Fluoro-4-(6-hydroxymethyl-4-methyl-2-propyl-benzoimidazol-1-ylmethyl)-benzoic acid methyl ester

HRID 1496713Notes

Reaction equation

HRID 1496713 reaction equation
[CH3:1][C:2]1[C:7]2[N:8]=[C:9]([CH2:11][CH2:12][CH3:13])[NH:10][C:6]=2[CH:5]=[C:4]([CH2:14][OH:15])[CH:3]=1.[H-].[Na+].[CH3:18][O:19][C:20](=[O:30])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27]Br)=[CH:23][C:22]=1[F:29]>CN(C=O)C>[CH3:18][O:19][C:20](=[O:30])[C:21]1[CH:26]=[CH:25][C:24]([CH2:27][N:10]2[C:6]3[CH:5]=[C:4]([CH2:14][OH:15])[CH:3]=[C:2]([CH3:1])[C:7]=3[N:8]=[C:9]2[CH2:11][CH2:12][CH3:13])=[CH:23][C:22]=1[F:29]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 18759821methyl 4-(bromomethyl)-2-fluorobenzoateHCID 59868533(7-Methyl-2-propyl-3H-benzoimidazol-5-yl)methanol

Product 1

HCID 687231872-Fluoro-4-(6-hydroxymethyl-4-methyl-2-propyl-benzoimidazol-1-ylmethyl)-benzoic acid methyl esterYield 43.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

(7-Methyl-2-propyl-3H-benzoimidazol-5-yl)methanol (3 g, 15 mmol; prepared as described in Preparation 7) was dissolved in 20 mL of dry DMF. The solution was cooled to 0° C. and sodium hydride (598 mg, 15 mmol, 60 wt % in mineral oil) was added. The mixture was stirred for 30 minutes. 4-Bromomethyl-2-fluorobenzoic acid methyl ester (3.7 g, 15 mmol; prepared as described in Preparation 3) in 50 mL of DMF was added, and the mixture was warmed to room temperature and stirred for 10 minutes. The solution was partitioned between EtOAc (300 mL) and 150 mL 10% LiCl (aqueous). The organic layer was separated, dried over MgSO4 and concentrated. The concentrate was flash chromatographed to produce Intermediate (8a) as a clear oil (2.4 g). MS m/z: [M+H+] calcd for C21H23FN2O3, 371.7. found 371.0.

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. stirringstirred for 10 minutes
  3. customThe solution was partitioned between EtOAc (300 mL) and 150 mL 10% LiCl (aqueous)
  4. customThe organic layer was separated
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. customchromatographed

Sources & evidence

ORD record
ord-827e9c3771eb44239d13a2c1c8ad1312
Source dataset
uspto-grants-2015_12
Patent number
US09198899B2

Reaction notes

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