Triethylamine → (S)-methyl 6-(2-(methoxycarbonyl)azetidin-1-yl)-5-nitronicotinate
Reaction equation
Cl.[NH:2]1[CH2:5][CH2:4][C@H:3]1[C:6]([O:8][CH3:9])=[O:7].C(N(CC)CC)C.Cl[C:18]1[C:27]([N+:28]([O-:30])=[O:29])=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][N:19]=1>O1CCCC1>[CH3:9][O:8][C:6]([C@@H:3]1[CH2:4][CH2:5][N:2]1[C:18]1[C:27]([N+:28]([O-:30])=[O:29])=[CH:26][C:21]([C:22]([O:24][CH3:25])=[O:23])=[CH:20][N:19]=1)=[O:7]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
(S)-methyl azetidine-2-carboxylate hydrochloride (1 g, 6.60 mmol) was diluted with Tetrahydrofuran (Volume: 20 ml) and treated with TRIETHYLAMINE (0.919 ml, 6.60 mmol). The reaction mixture was stirred vigorously and sonicated periodically, until a fine suspension resulted. This was stirred for 1 h and filtered through a small plug of celite. The plug was washed well with THF (20 mL) and the combined filtrate and washes were treated with methyl 6-chloro-5-nitronicotinate (0.714 g, 3.30 mmol). The reaction mixture was concentrated in vacuo and heated briefly (5 min) to 80° C. LCMS showed complete conversion. The reaction mixture was diluted with DCM (10 mL) and purified using flash column chromatography on silica gel (80 g SiO2, 20-30% ethyl acetate in hexanes) to afford the title compound (S)-methyl 6-(2-(methoxycarbonyl)azetidin-1-yl)-5-nitronicotinate (0.90 g, 3.05 mmol, 92% yield) as a yellow oil. [M+H] calc'd for C12H13N3O6, 295; found, 295.
Workup
- customsonicated periodically, until a fine suspension
- customresulted
- stirringThis was stirred for 1 h
- filtrationfiltered through a small plug of celite
- washThe plug was washed well with THF (20 mL)
- concentrationThe reaction mixture was concentrated in vacuo
- additionThe reaction mixture was diluted with DCM (10 mL)
- custompurified
Sources & evidence
- ORD record
- ord-50196dee100c4ba6b5df13ec117d7998
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08450323B2
Reaction notes
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