Cyclohexanone → 5-(1-hydroxycyclohex-1-yl)-3-(2-pyrrolidinylethyl)-1H-indole

HRID 609734Notes

Reaction equation

HRID 609734 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.C([Li])(C)(C)C.CCCCC.[C:28]1(=[O:34])[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1>CCOCC>[OH:34][C:28]1([C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3[CH2:11][CH2:12][N:13]2[CH2:17][CH2:16][CH2:15][CH2:14]2)[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 7967CyclohexanoneHCID 8003PentaneHCID 158384855-Bromo-3-[2-(pyrrolidin-1-yl)ethyl]-1H-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 699487065-(1-hydroxycyclohex-1-yl)-3-(2-pyrrolidinylethyl)-1H-indoleYield 36.2%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-bromo-3-(2-pyrrolidinylethyl)-1H-indole (Example 3b, 303 mg, 1.03 mmol) in ether (12.5 mL) was added to KH (42.9 mg, 1.07 mmol) at 0° C. After stirring at 0° C. for 20 minutes, the reaction mixture was cooled to -78° C. and a solution of tert-butyllithium in pentane (1.7 M, 0.22 mL, 2.1 mmol) was added dropwise. The reaction mixture was stirred at -78° C. for 30 minutes prior to the addition of cyclohexanone (0.22 mL, 2.1 mmol). The reaction was quenched by the addition of pH 7 buffer and the product was extracted into ethyl acetate, washed with water and brine, and dried over sodium sulfate. After removal of the solvent in vacuo, flash chromatography (silica, 5-10% 2M methanolic ammonia in dichloromethane) yielded 5-(1-hydroxycyclohex-1-yl)-3-(2-pyrrolidinylethyl)-1H-indole (116.4 mg, 36%); HRMS-FAB+ for C20H28N2O: calculated MH+ :313.22800; found MH+ :313.23151.

Workup

  1. temperaturethe reaction mixture was cooled to -78° C.
  2. stirringThe reaction mixture was stirred at -78° C. for 30 minutes
  3. customThe reaction was quenched by the addition of pH 7 buffer
  4. extractionthe product was extracted into ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over sodium sulfate
  7. customAfter removal of the solvent in vacuo, flash chromatography (silica, 5-10% 2M methanolic ammonia in dichloromethane)

Sources & evidence

ORD record
ord-6e4a14e1dce44ab7b7f0dcba76ad771e
Source dataset
uspto-grants-1999_12
Patent number
US05998438

Reaction notes

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