Water → 2-Fluoro-5-[[4-(1H-imidazol-1-yl)phenyl]methyl]-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acid

HRID 2255067Notes

Reaction equation

HRID 2255067 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]1[CH2:11][CH:12]([CH2:16][C:17]([OH:19])=[O:18])[CH2:13][CH2:14][CH2:15][C:5]2=1.[H-].[Na+].Cl.Cl[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH:35]=[CH:34][N:33]=[CH:32]2)=[CH:27][CH:26]=1.O>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:24][C:25]1[CH:26]=[CH:27][C:28]([N:31]3[CH:35]=[CH:34][N:33]=[CH:32]3)=[CH:29][CH:30]=1)[C:6]1[CH2:11][CH:12]([CH2:16][C:17]([OH:19])=[O:18])[CH2:13][CH2:14][CH2:15][C:5]2=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 197416342-Fluoro-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acidHCID 197946621-[4-(chloromethyl)phenyl]-1H-imidazole hydrochloride

Product 1

HCID 99317812-Fluoro-5-[[4-(1H-imidazol-1-yl)phenyl]methyl]-5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acidYield 59.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 122 mg of 2-fluoro- 5,6,7,8,9,10-hexahydrocyclohept[b]indole-7-acetic acid in 20 ml of dry DMF is cooled at 0° C., and treated with 102 mg of 55% NaH. The reaction mixture is stirred for 60 minutes at 0° C., then 160 mg of 1-[4-(chloro-methyl)phenyl]-1H-imidazole hydrochloride are added portionwise at 0° C. After stirring at room temperature for 16 hours the mixture is poured into water and washed with methylene chloride. The aqueous solution is neutralized with diluited HCl and extracted with methylene chloride. The organic layer is dried over sodium sulfate and evaporated to dryness. The residue, washed with acetone and dried, yields 116 mg of the title compound m.p. 237° C.

Workup

  1. stirringAfter stirring at room temperature for 16 hours the mixture
  2. washwashed with methylene chloride
  3. extractionextracted with methylene chloride
  4. dry with materialThe organic layer is dried over sodium sulfate
  5. customevaporated to dryness
  6. washThe residue, washed with acetone
  7. customdried

Sources & evidence

ORD record
ord-bcbbe1bc21ca46178cf9a3685bb13557
Source dataset
uspto-grants-1993_08
Patent number
US05238953

Reaction notes

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