Benzyl Bromide → HCID 54067774, compound

HRID 1870970Notes

Reaction equation

HRID 1870970 reaction equation
C([Li])CCC.C([O:13][C:14]1[CH:15]=[C:16]2[C:20](=[CH:21][CH:22]=1)[N:19]([S:23]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=[O:25])=[O:24])[CH:18]=[C:17]2[CH2:32][C@H:33]1[CH2:37][CH2:36][CH2:35][N:34]1[CH3:38])C1C=CC=CC=1.[CH2:39](Br)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1>C1COCC1>[CH2:39]([C:18]1[N:19]([S:23]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)(=[O:24])=[O:25])[C:20]2[C:16]([C:17]=1[CH2:32][C@H:33]1[CH2:37][CH2:36][CH2:35][N:34]1[CH3:38])=[CH:15][C:14]([OH:13])=[CH:22][CH:21]=2)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 54008280HCID 54008280, compoundHCID 178418339Butyllithium

Product 1

HCID 54067774HCID 54067774, compoundYield 52.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

n-Butyllithium (0.10 mL, 1.45M in hexane, 0.14 mmol) was added to a solution of (R)-5-benzyloxy-3-(1-methyl-2-pyrrolidinylmethyl)-1-phenylsulfonylindole (Example 7e, 24 mg, 0.052 mmol) in THF (2 mL) at -78° C.; the temperature was raised to 0° C. and the mixture was stirred for 20 min. After recooling to -78° C., benzyl bromide (18 μL, 0.15 mmol) was added and the mixture was stirred for 1 h at 78° C.; then 15 min. without cooling prior to quenching with water and extraction with ethyl acetate. The organic layer was washed sequentially with water and brine, and dried over sodium sulfate. Palladium on carbon (10%) was added to a solution of the crude product in methanol (2 mL) and the mixture was stirred under an atmosphere of hydrogen for 1.5 h. Removal of the catalyst by filtration followed by flash chromatography (silica gel, 0-10% 2M methanolic ammonia in dichloromethane) yielded (R)-2-benzyl-5-hydroxy-3-(1-methyl-2-pyrrolidinylmethyl)-1-phenylsulfonylindole (12.5 mg, 40%; HRMS-FAB+ for C27H28N2O3S calculated MH+ :461.18988; found MH+ :461.18724).

Workup

  1. customAfter recooling to -78° C.
  2. stirringthe mixture was stirred for 1 h at 78° C.
  3. temperaturethen 15 min. without cooling
  4. customto quenching with water and extraction with ethyl acetate
  5. washThe organic layer was washed sequentially with water and brine
  6. dry with materialdried over sodium sulfate
  7. additionPalladium on carbon (10%) was added to a solution of the crude product in methanol (2 mL)
  8. stirringthe mixture was stirred under an atmosphere of hydrogen for 1.5 h
  9. customRemoval of the catalyst
  10. filtrationby filtration

Sources & evidence

ORD record
ord-7b6a0ad2a7fb4e3dbf8001ab44e9f9f1
Source dataset
uspto-grants-2000_08
Patent number
US06100291

Reaction notes

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