Chloroacetyl chloride → 7-fluoro-3,4-dihydro-2H-1,4-benzoxazin-3-one

HRID 518971Notes

Reaction equation

HRID 518971 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[OH:9].C([O-])([O-])=O.[K+].[K+].Cl[CH2:17][C:18](Cl)=[O:19]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CC#N>[F:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:18](=[O:19])[CH2:17][O:9][C:3]=2[CH:4]=1

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 1857632-Amino-5-fluorophenol

Product 1

HCID 137312957-fluoro-3,4-dihydro-2H-1,4-benzoxazin-3-oneYield 87.2%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6342AcetonitrileSolvent

Procedure

To a suspension of 2-amino-5-fluorophenol (Alfa, 15.00 g, 118 mmol), K2CO3 (48.9 g, 354 mmol) and tetrabutyl-ammonium bromide (3.80 g, 11.80 mmol) in MeCN (200 mL) was added 2-chloroacetyl chloride (14.66 g, 130 mmol) dropwise at 0° C. The reaction mixture was warmed to rt and then heated at reflux overnight. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The solid was collected, washed with water (100 mL) and dried in vacuo to give 7-fluoro-4H-benzo[1,4]oxazin-3-one as a pale solid (17.2 g, 87%). 1H NMR (DMSO-d6, 400 MHz): δ10.71 (s, 1H), 6.84-6.88 (m, 2H), 6.76-6.81 (m, 1H), 4.57 (s, 2H).

Workup

  1. temperatureheated
  2. temperatureat reflux overnight
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. concentrationconcentrated in vacuo
  5. customThe solid was collected
  6. washwashed with water (100 mL)
  7. customdried in vacuo

Sources & evidence

ORD record
ord-79a0f26f02b9457f8813723be92bfeb5
Source dataset
uspto-grants-2015_08
Patent number
US09115151B2

Reaction notes

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