Water → HCID 178480509, compound

HRID 2404469Notes

Reaction equation

HRID 2404469 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]([C:10]2[NH:14][C:13]3[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:12]=3[N:11]=2)[OH:9])[CH:5]=[CH:6][CH:7]=1.[CH3:20][N:21]1[CH2:26][CH2:25][CH:24](O)[CH2:23][CH2:22]1.O.[OH-].[Na+]>CS(O)(=O)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]([O:9][CH:24]2[CH2:25][CH2:26][N:21]([CH3:20])[CH2:22][CH2:23]2)[C:10]2[NH:14][C:13]3[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:12]=3[N:11]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 660484-Piperidinol, 1-methyl-HCID 178519455HCID 178519455, compound

Product 1

HCID 178480509HCID 178480509, compound

Reagents, catalysts & solvents 1

HCID 6395Methanesulfonic AcidSolvent

Procedure

A mixture of (3-bromophenyl)(5-fluoro-1H-benzimidazol-2-yl)methanol (example 437E, 3.30 g) and 1-methylpiperidin-4-ol (2.37 g) in methanesulfonic acid (10 mL) is heated overnight in a sealed tube at a temperature close to 140° C. The mixture is cooled back to room temperature, poured into water which is then made alkaline with concentrated sodium hydroxide solution. The aqueous phase is extracted with ethyl acetate. Pooled extracts are dried over magnesium sulfate, concentrated under reduced pressure. The residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0 to 90/10/1) to afford 2-[(3-bromophenyl)(1-methylpiperidin-4-yloxy)methyl]-5-fluoro-1H-benzimidazole. 1H NMR: 9.92 (sl, 1H), 7.60 (s, 1H), 7.55-6.85 (m, 6H), 5.80 (s, 1H), 3.65-3.50 (m, 1H), 2.80-2.65 (m, 2H), 2.34 (s, 3H), 2.15-1.65 (m, 6H).

Workup

  1. temperatureis heated overnight in a sealed tube at a temperature
  2. customclose to 140° C
  3. extractionThe aqueous phase is extracted with ethyl acetate
  4. dry with materialPooled extracts are dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by column chromatography over silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0 to 90/10/1)

Sources & evidence

ORD record
ord-ed450684c1bd4b389ca28dc1dfea4ba8
Source dataset
uspto-grants-2014_08
Patent number
US08802664B2

Reaction notes

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