Dimethylformamide → 1-(4-Fluorophenyl)-4-hydroxymethyl-5-methyl-2-(4-methylsulfonylphenyl)pyrrole

HRID 1937355Notes

Reaction equation

HRID 1937355 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)=[CH:11][CH:10]=[C:9]2[CH3:23])=[CH:4][CH:3]=1.P(Cl)(Cl)(Cl)=O.[OH-].[Na+].[BH4-].[Na+].CN([CH:36]=[O:37])C>CCO.O.C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]3[CH:18]=[CH:17][C:16]([S:19]([CH3:22])(=[O:21])=[O:20])=[CH:15][CH:14]=3)=[CH:11][C:10]([CH2:36][OH:37])=[C:9]2[CH3:23])=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 27657241-(4-Fluorophenyl)-2-methyl-5-(4-methylsulfonylphenyl)pyrroleHCID 4311764Sodium borohydride

Product 1

HCID 105463821-(4-Fluorophenyl)-4-hydroxymethyl-5-methyl-2-(4-methylsulfonylphenyl)pyrrole

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(4-fluorophenyl)-2-methyl-5-(4-methylsulfonylphenyl)pyrrole, 5, (in FIG. 6) (prepared as described in J. Med. Chem., 1997, 40, 1619) (1 mmol) in dry DMF (10 mL) at 0° C. is added phosphorus oxychloride (1 mmol). The reaction is monitored by tlc and when it is complete, the mixture is poured onto ice and made basic with aqueous sodium hydroxide. The product is isolated by extraction with CH2Cl2. The extract is dried and evaporated to afford a residue. To the residue, dissolved in EtOH (10 mL) is added sodium borohydride (100 mg). After one hour, the solution is added to water and extracted with ethyl acetate. The extract is washed with dilute HCl, dried and evaporated. The title compound 6 is purified and isolated by HPLC.

Workup

  1. additionthe mixture is poured onto ice
  2. customThe extract is dried
  3. customevaporated
  4. customto afford a residue
  5. extractionextracted with ethyl acetate
  6. washThe extract is washed with dilute HCl
  7. customdried
  8. customevaporated
  9. customThe title compound 6 is purified
  10. customisolated by HPLC

Sources & evidence

ORD record
ord-c8dd520e2ca34eb186ccdf36100287c4
Source dataset
uspto-grants-2002_05
Patent number
US06395724B1

Reaction notes

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