Triethylamine → 7,8-Difluoro-6-hydroxymethyl-4h-benzo[1,4]oxazin-3-one

HRID 495445Notes

Reaction equation

HRID 495445 reaction equation
C(N(CC)CC)C.[F:8][C:9]1[C:19]([C:20](O)=[O:21])=[CH:18][C:12]2[NH:13][C:14](=[O:17])[CH2:15][O:16][C:11]=2[C:10]=1[F:23].ClC(OCC(C)C)=O>C1COCC1>[F:8][C:9]1[C:19]([CH2:20][OH:21])=[CH:18][C:12]2[NH:13][C:14](=[O:17])[CH2:15][O:16][C:11]=2[C:10]=1[F:23]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 223266397,8-Difluoro-4h-benzo[1,4]oxazine-3-one-6-carboxylic acid

Product 1

HCID 223267117,8-Difluoro-6-hydroxymethyl-4h-benzo[1,4]oxazin-3-oneYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Triethylamine (2.4 mL, 17.3 mmol) was added to a suspension of 7,8-difluoro-4H-benzo[1,4]oxazine-3-one-6-carboxylic acid (3.6 g, 15.7 mmol) in anhydrous THF (250 mL). Isobutyl chloroformate (2.2 mL, 17.3 mmol) was added to the mixture at ice cold temperature over 0.5 hour. Stirring was continued for further 2 hours at room temperature. It was then cooled in ice and the solid was removed by filtration. The filtrate was added to a cold solution of sodium borohydride (3.2 g) in water. The mixture was stirred in cold for 1 hour before it was concentrated in vacuo to half and acidified with 2M hydrochloric acid. The resulting solid precipitate was collected by filtration and dried to give the title compound (1.15 g, 22%).

Workup

  1. temperatureIt was then cooled in ice
  2. customthe solid was removed by filtration
  3. additionThe filtrate was added to a cold solution of sodium borohydride (3.2 g) in water
  4. stirringThe mixture was stirred in cold for 1 hour before it
  5. concentrationwas concentrated in vacuo to half
  6. filtrationThe resulting solid precipitate was collected by filtration
  7. customdried

Sources & evidence

ORD record
ord-526d6ff1fb4f4497862e3ba23d2ff120
Source dataset
uspto-grants-2005_09
Patent number
US06939871B2

Reaction notes

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