6-Ethoxycarbonylmethoxy-5-nitro-nicotinic acid methyl ester → Methyl 2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate

HRID 2421880Notes

Reaction equation

C([O:3][C:4](=O)[CH2:5][O:6][C:7]1[C:16]([N+:17]([O-])=O)=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][N:8]=1)C>CC(O)=O.[Fe]>[O:3]=[C:4]1[CH2:5][O:6][C:7]2[N:8]=[CH:9][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:15][C:16]=2[NH:17]1

Participants

Conditions

Temperature: 70 °C

Procedure

To a solution of methyl 6-(2-ethoxy-2-oxoethoxy)-5-nitronicotinate (2.43 g, 8.55 mmol) in AcOH (50 mL) was added iron powder (1.910 g, 34.2 mmol). The reaction was heated to 70° C. and stirred at that temperature for 2 hours. The reaction was concentrated in vacuo and diluted with water (300 mL). The solution was adjusted to pH=6 by addition of solid K3PO4. The aqueous layer was extracted with EtOAc (8×200 mL) and the combined organics were dried over anhydrous Na2SO4 and concentrated in vacuo. Methyl 2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazine-7-carboxylate (1.24 g, 5.96 mmol, 69.7% yield) was isolated as an off-white solid and used without purification. LCMS (+ESI) m/z=209.0 [M+H]+; 1H-NMR (DMSO-d6) δ 11.0 (s, 1H), 8.35 (d, 1H), 7.67 (d, 1H), 4.90 (s, 2H), 3.85 (s, 3H).

Workup

concentrationThe reaction was concentrated in vacuo
additiondiluted with water (300 mL)
additionThe solution was adjusted to pH=6 by addition of solid K3PO4
extractionThe aqueous layer was extracted with EtOAc (8×200 mL)
dry with materialthe combined organics were dried over anhydrous Na2SO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-c9905ffd22a941ae8e2970738ee6922f
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07960377B2

Reaction notes

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