Benzenesulfonyl chloride → HCID 15462187, compound

HRID 1870965Notes

Reaction equation

HRID 1870965 reaction equation
C([Li])CCC.[CH:6]1([O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][CH:17]=[C:16]3[CH2:22][C@H:23]2[CH2:27][CH2:26][CH2:25][N:24]2[CH3:28])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.[C:29]1([S:35](Cl)(=[O:37])=[O:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1COCC1>[CH:6]1([O:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([S:35]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)(=[O:37])=[O:36])[CH:17]=[C:16]3[CH2:22][C@H:23]2[CH2:27][CH2:26][CH2:25][N:24]2[CH3:28])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1

Participants

5

Reactant 3

HCID 7369Benzenesulfonyl chlorideHCID 53631894HCID 53631894, compoundHCID 178418339Butyllithium

Product 1

HCID 15462187HCID 15462187, compoundYield 17%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

n-Butyllithium (0.19 mL, 1.45M in hexane, 0.28 mmol) was added to a solution of (R)-5-cyclohexyloxy-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indole (Example 3g, 77.1 mg, 0.25 mmol) in THF (1 mL) at -78° C.; the temperature was raised to 0 ° C. and the mixture was stirred for 40 min. After recooling to -78° C., phenylsulfonyl chloride (60 μL, 0.47 mmol) was added and the mixture was allowed to warm to room temperature slowly (overnight). The mixture was quenched with water (5 mL) and extracted into dichloromethane. The organic layer was washed sequentially with water and brine, and dried over sodium sulfate. Purification by flash chromatography (silica gel, 1-4% 2M methanolic ammonia in chloroform) yielded (R)-5-cyclohexyloxy-3-(1-methyl-2-pyrrolidinylmethyl)-1-phenylsulfonylindole (19.1 mg, 17%, HRMS-FAB+ for C26H32N2O3S: calculated MH+ :453.22119; found MH+ :453.22550).

Workup

  1. customAfter recooling to -78° C.
  2. temperatureto warm to room temperature slowly (overnight)
  3. customThe mixture was quenched with water (5 mL)
  4. extractionextracted into dichloromethane
  5. washThe organic layer was washed sequentially with water and brine
  6. dry with materialdried over sodium sulfate
  7. customPurification by flash chromatography (silica gel, 1-4% 2M methanolic ammonia in chloroform)

Sources & evidence

ORD record
ord-99d7d00017c74f899d49f0de2c911254
Source dataset
uspto-grants-2000_08
Patent number
US06100291

Reaction notes

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