Chloroacetyl chloride → 8-Acetyl-6-(benzyloxy)-2H-1,4-benzoxazin-3(4H)-one

HRID 1662955Notes

Reaction equation

HRID 1662955 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].[NH2:6][C:7]1[C:8]([OH:24])=[C:9]([C:21](=[O:23])[CH3:22])[CH:10]=[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>>[C:21]([C:9]1[C:8]2[O:24][CH2:2][C:3](=[O:4])[NH:6][C:7]=2[CH:12]=[C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:10]=1)(=[O:23])[CH3:22]

Participants

4

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 210728221-(3-Amino-5-(benzyloxy)-2-hydroxyphenyl)ethanone

Product 1

HCID 211001368-Acetyl-6-(benzyloxy)-2H-1,4-benzoxazin-3(4H)-one

Procedure

21.0 mL (258 mmol) chloroacetyl chloride are added dropwise to 60.0 g (233 mmol) 1-(3-amino-5-benzyloxy-2-hydroxyphenyl)-ethanone and 70.0 g (506 mmol) potassium carbonate while being cooled with the ice bath. Then the mixture is stirred overnight at ambient temperature and then for 6 hours at reflux temperature. The hot reaction mixture is filtered, then evaporated down to approx. 400 mL and combined with ice water. The precipitate obtained is suction filtered, dried and purified by chromatography on a short silica gel column (dichloromethane:methanol=99:1). The fractions containing the product are evaporated down, suspended in isopropanol/diisopropylether, suction filtered and washed with diisopropylether. Yield: 34.6 g (50%); mass spectroscopy [M+H]+=298.

Workup

  1. temperaturefor 6 hours at reflux temperature
  2. filtrationThe hot reaction mixture is filtered
  3. customevaporated down to approx. 400 mL
  4. customThe precipitate obtained
  5. filtrationfiltered
  6. customdried
  7. custompurified by chromatography on a short silica gel column (dichloromethane:methanol=99:1)
  8. additionThe fractions containing the product
  9. customare evaporated down
  10. filtrationsuction filtered
  11. washwashed with diisopropylether

Sources & evidence

ORD record
ord-73c33bc9265a48c09bf10ddd99b25b6e
Source dataset
uspto-grants-2011_10
Patent number
US08034809B2

Reaction notes

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