Chloroacetyl chloride → 7-Methoxy-2H-1,4-benzoxazin-3(4H)-one

HRID 885954Notes

Reaction equation

HRID 885954 reaction equation
CCN(C(C)C)C(C)C.Cl.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=1[OH:20].Cl[CH2:22][C:23](Cl)=[O:24].C(=O)([O-])[O-].[K+].[K+]>C1COCC1.CC#N>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]2[NH:11][C:23](=[O:24])[CH2:22][O:20][C:13]=2[CH:14]=1

Participants

7

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 81531Diisopropylethylamine2×HCID 122101842-Amino-5-methoxyphenol Hydrochloride

Product 1

HCID 116007707-Methoxy-2H-1,4-benzoxazin-3(4H)-oneYield 17%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

DIPEA (2.2 mL, 12.5 mmol) was added to 2-amino-5-methoxyphenol hydrochloride (1 g, 5.7 mmol) in THF (13 mL). The reaction mixture was cooled to 0° C., chloroacetyl chloride (0.5 mL, 6.3 mmol) was added portionwise and then stirred at 0° C. for 5 minutes. Further DIPEA (1.1 mL, 6.3 mmol) was added and the mixture was allowed to warm to r.t. and stirred for 3 days. The majority of the THF was removed in vacuo. EtOAc (50 mL) and water (50 mL) were added. The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organic fractions were washed with brine (20 mL), dried (MgSO4), filtered and the solvent was evaporated in vacuo. To a portion of the crude material (0.250 g, 1.159 mmol) in MeCN (6 mL) was added potassium carbonate (0.449 g, 3.246 mmol) followed by THF (2 mL). The reaction mixture was stirred at r.t. for 5 h and then concentrated in vacuo. Water (5 mL) was added and the solid collected by filtration, washed with water (3×5 mL) and dried in vacuo to give the title compound (0.173 g, 17%) as a red solid. δH (DMSO-d6) 10.53 (1H, br s), 6.80 (1H, d, J 8.5 Hz), 6.58-6.51 (2H, m), 4.52 (2H, s), 3.69 (3H, s). LCMS (ES+) 180.1 (M+H)+, RT 2.27 minutes (Method 1).

Workup

  1. temperatureto warm to r.t.
  2. stirringstirred for 3 days
  3. customThe majority of the THF was removed in vacuo
  4. additionEtOAc (50 mL) and water (50 mL) were added
  5. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  6. washthe combined organic fractions were washed with brine (20 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. customthe solvent was evaporated in vacuo
  10. stirringThe reaction mixture was stirred at r.t. for 5 h
  11. concentrationconcentrated in vacuo
  12. additionWater (5 mL) was added
  13. filtrationthe solid collected by filtration
  14. washwashed with water (3×5 mL)
  15. customdried in vacuo

Sources & evidence

ORD record
ord-d92a85612f1c4e08905c34455a9438c5
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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