Formaldehyde → 6-bromo-5-methyl-3-phenyl-2H-benzo[e][1,3]oxazin-4(3H)-one

HRID 661848Notes

Reaction equation

HRID 661848 reaction equation
[Br:1][C:2]1[C:3]([CH3:18])=[C:4]([C:14]([OH:17])=[CH:15][CH:16]=1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:6].[CH2:19]=O>C(O)(C(F)(F)F)=O>[Br:1][C:2]1[CH:16]=[CH:15][C:14]2[O:17][CH2:19][N:7]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:5](=[O:6])[C:4]=2[C:3]=1[CH3:18]

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 593749883-bromo-6-hydroxy-2-methyl-N-phenylbenzamide2×

Product 1

HCID 593750516-bromo-5-methyl-3-phenyl-2H-benzo[e][1,3]oxazin-4(3H)-oneYield 60%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-bromo-6-hydroxy-2-methyl-N-phenylbenzamide (Intermediate 16-1, 40 mg, 0.131 mmol) and paraformaldehyde (11.77 mg, 0.392 mmol) in TFA (1 mL) was heated at 100° C. for 4 h. The TFA was removed under vacuum, and the residue was diluted with EtOAc (80 mL), washed with NaHCO3 (aq) (10 mL), water (10 mL) and brine (10 mL), and dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 95:5 to 70:30 hexane-EtOAc) to give 6-bromo-5-methyl-3-phenyl-2H-benzo[e][1,3]oxazin-4(3H)-one (25 mg, 45%). 1H NMR (400 MHz, chloroform-d) δ 7.63 (1H, d, J=8.80 Hz), 7.37-7.50 (3H, m), 7.29-7.35 (2H, m), 6.81 (1H, d, J=8.80 Hz), 5.48 (2H, s), 2.80 (3H, s). Mass spectrum m/z 318, 320 (M+H)+.

Workup

  1. customThe TFA was removed under vacuum
  2. additionthe residue was diluted with EtOAc (80 mL)
  3. washwashed with NaHCO3 (aq) (10 mL), water (10 mL) and brine (10 mL)
  4. customdried
  5. concentrationconcentrated
  6. customThe residue was purified by column chromatography (
  7. washeluting with a gradient from 95:5 to 70:30 hexane-EtOAc)

Sources & evidence

ORD record
ord-5b5e5bd3ab83455bacb5f57a26b90244
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

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