Chloroacetyl chloride → 8-Methyl-2H-benzo[B][1,4]oxazin-3(4H)-one

HRID 885945Notes

Reaction equation

HRID 885945 reaction equation
Cl[CH2:2][C:3](Cl)=[O:4].[NH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[C:8]=1[OH:14].C(N(CC)CC)C>C1COCC1>[CH3:13][C:9]1[C:8]2[O:14][CH2:2][C:3](=[O:4])[NH:6][C:7]=2[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471Triethylamine2×HCID 4136576-Amino-o-cresol

Product 1

HCID 141741528-Methyl-2H-benzo[B][1,4]oxazin-3(4H)-oneYield 78.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of chloroacetyl chloride (0.71 mL, 8.94 mmol) in THF (5 mL) was added dropwise to a solution/suspension of 2-amino-6-methylphenol (1 g, 8.13 mmol) and triethylamine (1.24 mL, 8.94 mmol) in THF (50 mL) which had been pre-cooled in an ice-water bath. After stirring for 5 minutes a further portion of triethylamine (1.24 mL, 8.94 mmol) was added. The mixture was stirred and warmed to r. t. After 24 h the reaction was allowed to stand overnight. The mixture was concentrated in vacuo and the residue was partitioned between water (100 mL) and EtOAc (50 mL). Brine (20 mL) was added to the aqueous phase, and this was further extracted with EtOAc (50 mL). The combined organic fractions were dried (MgSO4), concentrated in vacuo, and purified by column chromatography (SiO2, 20-100% EtOAc/heptane) to give an orange-brown solid (1.04 g), which was dissolved in THF (10 mL) and triethylamine (2 mL), and the mixture left to stand for 3 days. The mixture was concentrated in vacuo and purified by column chromatography (SiO2, 10-50% EtOAc/heptane) to give a cream solid (0.6 g). This was dissolved in DCM (40 mL), and the solution was washed with aqueous NaOH (2M, 10 mL). The organic fraction was dried (MgSO4) and concentrated in vacuo to give the title compound (0.29 g, 22%) as a beige solid. LCMS (ES+) 164 (M+H)+, RT 2.61 minutes (Method 1).

Workup

  1. temperaturehad been pre-cooled in an ice-water bath
  2. additionwas added
  3. temperaturewarmed to r
  4. waitto stand overnight
  5. concentrationThe mixture was concentrated in vacuo
  6. customthe residue was partitioned between water (100 mL) and EtOAc (50 mL)
  7. additionBrine (20 mL) was added to the aqueous phase
  8. extractionthis was further extracted with EtOAc (50 mL)
  9. dry with materialThe combined organic fractions were dried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. custompurified by column chromatography (SiO2, 20-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-fa7835d7b78b488f80b89e36c0dd7dd8
Source dataset
uspto-grants-2012_08
Patent number
US08242116B2

Reaction notes

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