Dimethylformamide → 5-Hydroxy-7,8-dimethoxy-2-oxo-2,3-dihydro-1H-benzo[b]azepine-4-carboxylic acid ethyl ester

HRID 498985Notes

Reaction equation

C(O[C:4](=[O:25])[C:5]1[CH:10]=[C:9]([O:11][CH3:12])[C:8]([O:13][CH3:14])=[CH:7][C:6]=1[NH:15][C:16](=[O:24])[CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])C.CN(C)C=O.[H-].[Na+].[H][H]>C1(C)C=CC=CC=1.[Cl-].[Na+].O.O.C(O)(=O)C>[CH2:22]([O:21][C:19]([C:18]1[CH2:17][C:16](=[O:24])[NH:15][C:6]2[CH:7]=[C:8]([O:13][CH3:14])[C:9]([O:11][CH3:12])=[CH:10][C:5]=2[C:4]=1[OH:25])=[O:20])[CH3:23]

Participants

Conditions

Temperature: 80 °C

Procedure

A solution of 4,5-dimethoxy-2-[(4-ethoxy-1,4-dioxobutyl)amino]benzoic acid ethyl ester (5.940 g, 16 mmol) and N,N-dimethylformamide (7.5 ml) in toluene (60 ml) was added dropwise to a stirred suspension of powdered sodium hydride (80%, 2.57 g, 85.7 mmol) under argon in toluene (70 ml). After the hydrogen evolution had ceased, the mixture was stirred for 7 hours at 80° C. under argon, then cooled to 20° C. and acetic acid (5 ml) and water (40 ml) added dropwise in succession. Brine (100 ml) was added and the organic phase dried (magnesium sulphate) and evaporated to give the title compound as a white solid, (2.842 g, 55% yield), mp 218° C.; 1H-NMR (DMSO-d6, 300 MHz): δ (ppm)=12.7 (br s; 1 H), 7.96 (s; 1H), 7.3 (s; 1H), 6.49 (s; 1H), 4.32 (q; 2H), 3.95 and 3.93 (s; 6H), 3.1 (s; 2H), 1.38 (t; 3H).

Workup

temperaturecooled to 20° C.
dry with materialthe organic phase dried (magnesium sulphate)
customevaporated

Sources & evidence

ORD record: ord-461eec0d69e74da38787cfc8e6ec4e0a
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07767664B2

Reaction notes

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