Sodium hydride → (+)-3-(3,4-Difluorophenyl)-5-oxo-morpholine-4-carboxylic acid-4-nitro-phenyl ester

HRID 278900Notes

Reaction equation

HRID 278900 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[NH:14][C:13](=[O:15])[CH2:12][O:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[H-].[Na+].Cl[C:19]([O:21][C:22]1[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=1)=[O:20]>C1COCC1>[N+:28]([C:25]1[CH:24]=[CH:23][C:22]([O:21][C:19]([N:14]2[C:13](=[O:15])[CH2:12][O:11][CH2:10][CH:9]2[C:4]2[CH:5]=[CH:6][C:7]([F:8])=[C:2]([F:1])[CH:3]=2)=[O:20])=[CH:27][CH:26]=1)([O-:30])=[O:29]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 821294-Nitrophenyl chloroformateHCID 18623221HCID 18623221, compound

Product 1

HCID 15550626(+)-3-(3,4-Difluorophenyl)-5-oxo-morpholine-4-carboxylic acid-4-nitro-phenyl esterYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-(3,4-difluoro-phenyl)-morpholin-3-one (0.34 g, 1.57 mmol) in 10 mL of THF was added NaH (0.05 g, 1.9 mmol) and the resulting solution was stirred for 30 min. It was then transferred via a syringe into a solution of 4-nitrophenyl chloroformate in 20 mL of anhydrous THF at −78° C. under argon. The resulting solution was stirred for 2 hours after which the solvent was removed and the residue was purified by column chromatography on silica gel with 1:1 hexane/CH2Cl2 followed by CH2Cl2 to obtain 3-(3,4-difluorophenyl)-5-oxo-morpholine-4-carboxylic acid-4-nitro-phenyl ester as a colorless thick oil (0.31 g, 51%).

Workup

  1. stirringThe resulting solution was stirred for 2 hours after which the solvent
  2. customwas removed
  3. customthe residue was purified by column chromatography on silica gel with 1:1 hexane/CH2Cl2

Sources & evidence

ORD record
ord-8cb03d7a82334c768dd591591dbb937b
Source dataset
uspto-grants-2002_03
Patent number
US06362182B1

Reaction notes

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