Phenol → HCID 178480513, compound

HRID 572876Notes

Reaction equation

HRID 572876 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][S:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]([C:26]2[NH:30][C:29]3[CH:31]=[CH:32][C:33]([F:35])=[CH:34][C:28]=3[N:27]=2)[O:18][CH:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[CH:12]=1)(C)(C)C.C1(O)C=CC=CC=1.Cl[Si](C)(C)C>C(Cl)(Cl)Cl>[F:35][C:33]1[CH:32]=[CH:31][C:29]2[NH:30][C:26]([CH:17]([O:18][CH:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[C:13]3[CH:12]=[C:11]([S:10][CH2:9][CH2:8][NH2:7])[CH:16]=[CH:15][CH:14]=3)=[N:27][C:28]=2[CH:34]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 6397ChlorotrimethylsilaneHCID 178480516HCID 178480516, compound

Product 1

HCID 178480513HCID 178480513, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of (2-{3-[(5-fluoro-1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenylsulfanyl}ethyl)carbamic acid tert-butyl ester (example 437C, 386 mg) in chloroform (10 mL) are added phenol (750 mg) and chlorotrimethylsilane (814 mg). The mixture is heated at reflux for 2 h. The solvent and volatiles are removed under reduced pressure. The residue is basified by adding a solution of 1N sodium hydroxide. The aqueous phase is extracted by ethyl acetate. The organic phase is washed by water, then dried over magnesium sulfate and concentrated. The residue is purified by chromatography on silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0 to 90/10/1) to give 2-{3-[(5-fluoro-1H-benzimidazol-2-yl)(1-methylpiperidin-4-yloxy)methyl]phenylsulfanyl}ethylamine.

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 2 h
  3. customThe solvent and volatiles are removed under reduced pressure
  4. additionby adding a solution of 1N sodium hydroxide
  5. extractionThe aqueous phase is extracted by ethyl acetate
  6. washThe organic phase is washed by water
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue is purified by chromatography on silica gel (gradient dichloromethane/methanol/ammonia from 100/0/0 to 90/10/1)

Sources & evidence

ORD record
ord-08f19a5c0aac4660b5e3a4d3fa4a4367
Source dataset
uspto-grants-2015_05
Patent number
US09029357B2

Reaction notes

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