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

HRID 1811028Notes

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

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 chromatogaphy (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 (1 H, d, J=8.80 Hz), 7.37-7.50 (3 H, m), 7.29-7.35 (2 H, m), 6.81 (1 H, d, J=8.80 Hz), 5.48 (2 H, s), 2.80 (3 H, s). Mass spectrum m/z 318, 320 (M+H)+.

Workup

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

Sources & evidence

ORD record: ord-8ba3afde7b3d4e0baf4dcbc57594180c
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362065B2

Reaction notes

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