Methanol → 5-[4,6-Difluoro-5-(1-methyl-1H-indol-5-yl)-1H-benzoimidazol-2-yloxy]-2-methyl-benzoic acid

HRID 1945298Notes

Reaction equation

HRID 1945298 reaction equation
C[O:2][C:3](=[O:33])[C:4]1[CH:9]=[C:8]([O:10][C:11]2[NH:15][C:14]3[CH:16]=[C:17]([F:31])[C:18]([C:21]4[CH:22]=[C:23]5[C:27](=[CH:28][CH:29]=4)[N:26]([CH3:30])[CH:25]=[CH:24]5)=[C:19]([F:20])[C:13]=3[N:12]=2)[CH:7]=[CH:6][C:5]=1[CH3:32].CO.O.[OH-].[Na+]>C1COCC1>[F:20][C:19]1[C:13]2[N:12]=[C:11]([O:10][C:8]3[CH:7]=[CH:6][C:5]([CH3:32])=[C:4]([CH:9]=3)[C:3]([OH:33])=[O:2])[NH:15][C:14]=2[CH:16]=[C:17]([F:31])[C:18]=1[C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[N:26]([CH3:30])[CH:25]=[CH:24]2

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 14798Sodium Hydroxide2×HCID 686594755-[4,6-Difluoro-5-(1-methyl-1H-indol-5-yl)-1H-benzoimidazol-2-yloxy]-2-methyl-benzoic acid methyl ester

Product 1

HCID 452568635-[4,6-Difluoro-5-(1-methyl-1H-indol-5-yl)-1H-benzoimidazol-2-yloxy]-2-methyl-benzoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 5-[4,6-difluoro-5-(1-methyl-1H-indol-5-yl)-1H-benzoimidazol-2-yloxy]-2-methyl-benzoic acid methyl ester (655 mg, 1.464 mmol) in THF:MeOH:H2O (7 mL) was treated with sodium hydroxide (1N, 3 mL) at room temperature. After 3 h, another 3 mL of sodium hydroxide (1N) was added and stirred at room temperature for another 1.5 h, and at 50° C. for another 1.5 h. The cooled reaction solution was concentrated on a rotavapor and the resulting aqueous solution was neutralized with 1N hydrogen chloride (6 mL), and the resulting white solid was collected through filtration (washed with water) and dried under high vacuum to give the desired product as a white solid. LC-MS: calculated for C24H17F2N3O3 434.41, observed m/e 434.6 (M+H)+ (Rt 1.52 min). 1H NMR (300 MHz, DMSO-d6): δ 7.78-7.15 (m, 8H), 6.45 (d, J=3.3 Hz, 1H), 3.81 (s, 3H), 2.53 (s, 3H).

Workup

  1. waitat 50° C. for another 1.5 h
  2. customThe cooled reaction solution
  3. concentrationwas concentrated on a rotavapor
  4. filtrationthe resulting white solid was collected through filtration (washed with water)
  5. customdried under high vacuum

Sources & evidence

ORD record
ord-1ff539ae3f3e4265b0fe5de0c7da32d9
Source dataset
uspto-grants-2013_03
Patent number
US08394969B2

Reaction notes

Loading…