Water → 7-Benzenesulfonyl-4-(1-benzyl-pyrrolidin-3-yl)-3,4-dihydro-2H-benzo[1,4]oxazine

HRID 2224081Notes

Reaction equation

HRID 2224081 reaction equation
[H-].[Na+].[C:3]1([S:9]([C:12]2[CH:21]=[CH:20][C:15]3[NH:16][CH2:17][CH2:18][O:19][C:14]=3[CH:13]=2)(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:22]([N:29]1[CH2:33][CH2:32][CH:31](OS(C)(=O)=O)[CH2:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN(C)C=O>[C:3]1([S:9]([C:12]2[CH:21]=[CH:20][C:15]3[N:16]([CH:31]4[CH2:32][CH2:33][N:29]([CH2:22][C:23]5[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=5)[CH2:30]4)[CH2:17][CH2:18][O:19][C:14]=3[CH:13]=2)(=[O:11])=[O:10])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 98998111-Benzylpyrrolidin-3-yl methanesulfonateHCID 586415137-benzenesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazine

Product 1

HCID 586415207-Benzenesulfonyl-4-(1-benzyl-pyrrolidin-3-yl)-3,4-dihydro-2H-benzo[1,4]oxazineYield 40.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of sodium hydride (0.033 g. of a 60% dispersion in mineral oil, 0.834 mmol) in 3 mL dimethylformamide was added portionwise 7-benzenesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazine (0.200 g, 0.726 mmol), and the resulting suspension was stirred at room temperature for 10 minutes. Racemic methanesulfonic acid 1-benzyl-pyrrolidin-3-yl ester (0.259 g., 1.018 mmol) was added dropwise and the reaction mixture was heated to 65° C. for 21 hours. The reaction mixture was then poured into 100 mL water, and extracted three times with 50 mL ethyl acetate. The organic fraction was washed twice with 50 mL 10% aq. hydrogen chloride and once with 50 mL saturated sodium bicarbonate. The organic fraction was then dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography (2%-5% methanol in dichlormethane) to give 0.127 g (0.292 mmol, 40%) of 7-benzenesulfonyl-4-(1-benzyl-pyrrolidin-3-yl)-3,4-dihydro-2H-benzo[1,4]oxazine as a red oil. MS: 474 (M+ACN)+.

Workup

  1. temperaturethe reaction mixture was heated to 65° C. for 21 hours
  2. extractionextracted three times with 50 mL ethyl acetate
  3. washThe organic fraction was washed twice with 50 mL 10% aq. hydrogen chloride and once with 50 mL saturated sodium bicarbonate
  4. dry with materialThe organic fraction was then dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash chromatography (2%-5% methanol in dichlormethane)

Sources & evidence

ORD record
ord-32b9d76836cc4441b31987bb37a3e318
Source dataset
uspto-grants-2008_05
Patent number
US07378415B2

Reaction notes

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