Ethyl chloroformate → N-Ethylcarbamate 5-methoxy-8-methyl-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrole
Reaction equation
Cl[C:2]([O:4]CC)=[O:3].[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]2[CH:13]([CH3:21])[CH:14]3[CH2:18][NH:17][CH2:16][CH:15]3[C:19]=2[CH:20]=1>C1COCC1.O>[CH2:16]([NH:17][C:2](=[O:3])[O-:4])[CH3:15].[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]2[CH:13]([CH3:21])[CH:14]3[CH2:18][NH:17][CH2:16][CH:15]3[C:19]=2[CH:20]=1Participants
Procedure
Hydrogen sodium carbonate (11.7 g, 139 mmol) and ethyl chloroformate (3.2 mL, 33.4 mmol) were added to a solution of 5-methoxy-8-methyl-1,2,3,3a,8,8a-hexahydroindeno[1,2-c]pyrrole (from Example 1, Step E) (5.6 g, 27.8 mmol) in THF/H2O (140 mL, 1/1, v/v), and stirred overnight at room temperature. The reaction mixture was quenched by addition of an aqueous HCl solution (200 mL, 1.0 M) and the product was extracted with EtOAc (3×100 mL). The combined organic extracts were dried over MgSO4 and concentrated. The crude product was purified by column chromatography (SiO2) using a 0-35% ethyl acetate-hexanes gradient to afford 2.7 g (35%) of the subtitle compound. 1H NMR (CDCl3 300 MHz)*7.07 (d, 1H), 6.78 (m, 2H), 4.09 (m, 2H), 3.79 (m, 5H), 3.63 (m, 1H), 3.52 (m, 1H), 3.32 (m, 1H), 3.07 (m, 1H), 2.95 (m, 1H), 1.26 (m, 6H) ppm. MS calculated for C16H21NO3+H: 276, observed: 276.
Workup
- customThe reaction mixture was quenched by addition of an aqueous HCl solution (200 mL, 1.0 M)
- extractionthe product was extracted with EtOAc (3×100 mL)
- dry with materialThe combined organic extracts were dried over MgSO4
- concentrationconcentrated
- customThe crude product was purified by column chromatography (SiO2)
Sources & evidence
- ORD record
- ord-19c4822c60184c0293b563aef8265e95
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096520B2
Reaction notes
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