Ethyl chloroformate → 4-ethyl 2-methyl 6-cyano-2H-benzo[b][1,4]oxazine-2,4(3H)-dicarboxylate

HRID 383325Notes

Reaction equation

[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH:10]([C:12]([O:14][CH3:15])=[O:13])[CH2:9][NH:8][C:7]=2[CH:16]=1)#[N:2].C([O-])([O-])=O.[K+].[K+].Cl[C:24]([O:26][CH2:27][CH3:28])=[O:25]>ClCCl>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH:10]([C:12]([O:14][CH3:15])=[O:13])[CH2:9][N:8]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:7]=2[CH:16]=1)#[N:2]

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of methyl 6-cyano-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate (629 mg, 2.88 mmol) and K2CO3 (1195 mg, 8.65 mmol) in dichloromethane (30 mL) was cooled at 0° C. and ethyl chloroformate (0.76 mL, 7.8 mmol) was added. The mixture was heated at reflux temperature for 30 h. The reaction was cooled and extracted with dichloromethane (3×20 mL), dried over Na2SO4 and concentrated. The product 4-ethyl 2-methyl 6-cyano-2H-benzo[b][1,4]oxazine-2,4(3H)-dicarboxylate was obtained as a yellow oil (670 mg, 80% yield) after purification by silica gel column chromatography (0-25% ethyl acetate/hexanes). 1H NMR (400.0 MHz, DMSO-d6) δ 8.11 (s, 1H), 7.53 (dd, J=2.0, 8.5 Hz, 1H), 7.18 (d, J=8.5 Hz, 1H), 5.36 (t, J=3.3 Hz, 1H), 4.39 (dd, J=3.5, 14.1 Hz, 1H), 4.27-4.15 (m, 2H), 3.76 (dd, J=3.2, 14.1 Hz, 1H), 3.71-3.67 (m, 3H), 1.25 (t, J=7.1 Hz, 3H).

Workup

temperatureThe mixture was heated
temperatureat reflux temperature for 30 h
temperatureThe reaction was cooled
extractionextracted with dichloromethane (3×20 mL)
dry with materialdried over Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-21b7664f3f444fd987947262c1d2bfda
Source dataset: uspto-grants-2013_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08367660B2

Reaction notes

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