Ethyl chloroformate → 6-bromo-5-methyl-3-phenyl-2H-benzo[e][1,3]oxazine-2,4(3H)-dione

HRID 1811029Notes

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].Cl[C:20](OCC)=[O:21]>N1C=CC=CC=1.CCOC(C)=O>[Br:1][C:2]1[CH:16]=[CH:15][C:14]2[O:17][C:20](=[O:21])[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

Step 1 A solution of 3-bromo-6-hydroxy-2-methyl-N-phenylbenzamide (Intermediate 16-1, 40 mg, 0.131 mmol) in pyridine (1 mL) was treated with ethyl chloroformate (0.015 mL, 0.157 mmol) at rt and the mixture was heated to 100° C. for 2 h. Additional ethyl chloroformate (0.015 mL, 0.157 mmol) was added and the mixture was stirred at 100° C. for 15 h. The mixture was cooled and diluted with EtOAc (80 mL), and the solution was washed with NaHCO3 (aq) (10 mL), water (2×10 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]oxazine-2,4(3H)-dione (19 mg, 44%). 1H NMR (400 MHz, chloroform-d) δ 7.90 (1 H, d, J=9.02 Hz), 7.43-7.68 (3 H, m), 7.27-7.40 (2 H, m), 7.12 (1 H, d, J=8.80 Hz), 2.90 (3H, s). Mass spectrum m/z 332, 334 (M+H)+.

Workup

temperatureThe mixture was cooled
washthe solution was washed with NaHCO3 (aq) (10 mL), water (2×10 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-a9d621520743401697e9cd1e6d0bc13c
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362065B2

Reaction notes

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