Sodium hydride → (r)-5,11-Dihydro-5-[1-(t-butoxycarbonyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine

HRID 411963Notes

Reaction equation

HRID 411963 reaction equation
[H-].[Na+].[CH:3]1[C:13]2[CH2:12][O:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[NH:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.S(C1C=CC(C)=CC=1)(O[CH2:22][C@H:23]1[CH2:27][CH2:26][CH2:25][N:24]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])(=O)=O.S(=O)(=O)(O)[O-].[K+]>CCCCCC.CS(C)=O>[C:31]([O:30][C:28]([N:24]1[CH2:25][CH2:26][CH2:27][C@@H:23]1[CH2:22][N:8]1[C:7]2[CH:6]=[CH:5][CH:4]=[CH:3][C:13]=2[CH2:12][O:11][C:10]2[CH:14]=[CH:15][CH:16]=[CH:17][C:9]1=2)=[O:29])([CH3:34])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 110847985,11-Dihydrodibenzo[b,e][1,4]oxazepineHCID 11760051(R)-tert-Butyl 2-((tosyloxy)methyl)pyrrolidine-1-carboxylate

Product 1

HCID 69947237(r)-5,11-Dihydro-5-[1-(t-butoxycarbonyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepineYield 22.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
50 °C

Procedure

60% sodium hydride (1.44 g, 36 mmol) was washed with hexane under argon atmosphere, and then suspended in dimethyl sulfoxide (100 ml). 5,11-dihydrodibenzo[b,e][1,4]oxazepine [H. L. Yale, et al. J. Med. Chem., 7, 609 (1964)] (6.0 g, 30 mmol) was added to the obtained suspension, and the resultant mixture was stirred at 50° C. for 60 minutes. A solution of (R)-N-t-butoxycarbonyl-2-pyrrolidinylmethyl tosylate (12.8 g, 36 mmol) in dimethyl sulfoxide (60 ml) was dropped therein and the obtained mixture was stirred at 50° C. for 3 hours. The reaction solution was poured into 5% aqueous potassium bisulfate solution cooled with ice/water. After the extraction with ethyl acetate, the organic layer was washed with saturated aqueous sodium bicarbonate solution and then with saturated aqueous sodium chloride solution and dried. The solvent was evaporated under reduced pressure. The residue was treated by the column chromatography. After the elusion with a mixed solvent of ethyl acetate and hexane (1:11), the solvent was evaporated under reduced pressure to obtain (R)-5,11-dihydro-5-[1-(t-butoxycarbonyl)-2-pyrrolidinylmethyl]dibenzo[b,e][1,4]oxazepine (2.57 g, 22%).

Workup

  1. extractionAfter the extraction with ethyl acetate
  2. washthe organic layer was washed with saturated aqueous sodium bicarbonate solution
  3. dry with materialwith saturated aqueous sodium chloride solution and dried
  4. customThe solvent was evaporated under reduced pressure
  5. additionThe residue was treated by the column chromatography
  6. customAfter the elusion with a mixed solvent of ethyl acetate and hexane (1:11), the solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-a840db788c5b435b839ff09eda903847
Source dataset
uspto-grants-2003_05
Patent number
US06562808B1

Reaction notes

Loading…