Water → HCID 86724968, compound

HRID 1847043Notes

Reaction equation

HRID 1847043 reaction equation
C1(C)C=CC(S(Cl)(=O)=O)=CC=1.O[CH2:13][C@@H:14]1[CH2:18][N:17]([C:19]2[CH:20]=[CH:21][C:22]3[O:27][CH2:26][C:25](=[O:28])[NH:24][C:23]=3[CH:29]=2)[C:16](=[O:30])[CH2:15]1.[N-:31]=[N+:32]=[N-:33].[Na+].O>N1C=CC=CC=1.ClCCl>[N:31]([CH2:13][C@@H:14]1[CH2:18][N:17]([C:19]2[CH:20]=[CH:21][C:22]3[O:27][CH2:26][C:25](=[O:28])[NH:24][C:23]=3[CH:29]=2)[C:16](=[O:30])[CH2:15]1)=[N+:32]=[N-:33]

Participants

7

Reactant 4

HCID 962WaterHCID 73974-Toluenesulfonyl chlorideHCID 33557Sodium AzideHCID 86724967HCID 86724967, compound

Product 1

HCID 86724968HCID 86724968, compoundYield 65.3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

p-Toluenesulfonyl chloride (611 mg, 3.20 mmol) was added at room temperature to a solution of 6-[(4S)-4-(hydroxymethyl)-2-oxopyrrolidin-1-yl]-2H-1,4-benzoxazin-3(4H)-one (420 mg, 1.60 mmol) in pyridine (5 ml) and the mixture was stirred for 24 hours. The reaction solution was concentrated under reduced pressure and the obtained resultant was dissolved in dichloromethane and washed with 1N hydrochloric acid. The aqueous layer was extracted with dichloromethane and the organic layer was washed sequentially with water and a saturated sodium hydrogen carbonate aqueous solution. The organic layer was dried over anhydrous sodium sulfate, the drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The obtained brown solid was dissolved in N,N-dimethylformamide (5 mL), sodium azide (208 mg, 3.20 mmol) was added thereto and the mixture was stirred at 80° C. for 2 hours. After adding water, the reaction solution was poured into a mixture of dichloromethane and a saturated sodium hydrogen carbonate aqueous solution and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate, the drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. Dichloromethane was added to the obtained residue to prepare a slurry and the solid was collected by filtration to yield 300 mg of the title compound in the form of a light yellow solid. The residue obtained by concentrating the filtrate was purified by silica gel column chromatography (dichloromethane/methanol) to yield 132 mg of the title compound in the form of a light yellow solid. Total yield 432 mg (94%).

Workup

  1. concentrationThe reaction solution was concentrated under reduced pressure
  2. customthe obtained resultant
  3. washwashed with 1N hydrochloric acid
  4. extractionThe aqueous layer was extracted with dichloromethane
  5. washthe organic layer was washed sequentially with water
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. customthe drying agent was removed by filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. dissolutionThe obtained brown solid was dissolved in N,N-dimethylformamide (5 mL)
  10. stirringthe mixture was stirred at 80° C. for 2 hours
  11. extractiona saturated sodium hydrogen carbonate aqueous solution and extracted with dichloromethane
  12. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  13. customthe drying agent was removed by filtration
  14. concentrationthe filtrate was concentrated under reduced pressure
  15. additionDichloromethane was added to the obtained residue
  16. customto prepare a slurry
  17. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-ec161cf5ed074f21a19bc6d663cfa479
Source dataset
uspto-grants-2015_02
Patent number
US08952010B2

Reaction notes

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