N,N,N',N',N'',N''-Hexamethylmethanetriamine → 4,5,6,7-Tetrahydro-1-oxa-2,7-diaza-cyclopenta[e]azulene-9-carboxylic acid ethyl ester

HRID 497404Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:22](=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][C:8]=2[N:9](C(OC(C)(C)C)=O)[CH:10]=1)=[O:5])[CH3:2].[CH3:24][N:25](C(N(C)C)N(C)C)C.Cl.NO>CCO>[CH2:1]([O:3][C:4]([C:6]1[C:7]2[C:22]3[O:23][N:25]=[CH:24][C:21]=3[CH2:20][CH2:19][CH2:18][C:8]=2[NH:9][CH:10]=1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 60 °C

Procedure

In a sealed tube, 4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[b]pyrrole-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (2.6 mmol) and tris(dimethylamino)methane (5.2 mmol) are combined and heated at 60° C. for 3 hours. After cooling to RT the volatile material is removed in vacuo. To the residue were added hydroxylamine hydrochloride (7.8 mmol) and 7 mL EtOH. The mixture is heated at 100° C. for 16 hours. The solvent is evaporated in vacuo and the residue is taken up in CH2Cl2 and washed two times with NaHCO3 (aq). The organic layer is dried over Na2SO4 and evaporated in vacuo and the residue chromatographed using 10% MeOH in CH2Cl2 as mobile phase to yield 4,5,6,7-tetrahydro-1-oxa-2,7-diaza-cyclopenta[e]azulene-9-carboxylic acid ethyl ester as a white solid (76%). 1H NMR (CDCl3) 1.19 (t, 3H), 1.95-2.07 (m, 2H), 2.78 (t, 2H), 2.95 (t, 2H), 4.38 (q, 2H), 7.26 (s, 1H), 8.03 (s, 1H), 8.77 (s, 1H).

Workup

temperatureAfter cooling to RT the volatile material
customis removed in vacuo
temperatureThe mixture is heated at 100° C. for 16 hours
customThe solvent is evaporated in vacuo
washwashed two times with NaHCO3 (aq)
dry with materialThe organic layer is dried over Na2SO4
customevaporated in vacuo
customthe residue chromatographed

Sources & evidence

ORD record: ord-078a799ba5c243a6846878e917dd4807
Source dataset: uspto-grants-2005_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06949562B2

Reaction notes

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