Methylamine → Ethyl 2-(methylamino)quinoline-6-carboxylate
Reaction equation
FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[CH2:16]([O:18][C:19]([C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[N+:27]([O-])=[CH:26][CH:25]=[CH:24]2)=[O:20])[CH3:17].[CH3:32][NH2:33].O1CCCC1>ClCCl>[CH3:32][NH:33][C:26]1[CH:25]=[CH:24][C:23]2[C:28](=[CH:29][CH:30]=[C:21]([C:19]([O:18][CH2:16][CH3:17])=[O:20])[CH:22]=2)[N:27]=1Participants
Conditions
- Temperature
- -70 °C
Procedure
Trifluoromethanesulfonic anhydride (1.92 mL, 11.4 mmol) was added dropwise to a −70° C. solution of 6-(ethoxycarbonyl)quinoline 1-oxide (2.25 g, 10.4 mmol) in dichloromethane (150 mL). The mixture was stirred at −70° C. for 5 minutes. Then a solution of methylamine in tetrahydrofuran (31 mL, 62 mmol, 2 M) was added dropwise. The mixture was stirred at −70° C. for 5 minutes. The reaction was quenched with water (20 mL). The layers were separated and the aqueous was extracted with dichloromethane (3×30 mL). The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography gave the title compound (850 mg, 35%) as a yellow solid. 1H NMR (400 MHz, CDCl3, δ): 8.33 (d, 1H), 8.16-8.13 (m, 1H), 7.90-7.87 (d, 1H), 7.70-7.67 (d, 1H), 6.68 (d, 1H), 5.30 (br. s., 1H), 4.43-4.38 (q, 2H), 3.13-3.12 (d, 3H), 1.44-1.40 (m, 3H).
Workup
- stirringThe mixture was stirred at −70° C. for 5 minutes
- customThe reaction was quenched with water (20 mL)
- customThe layers were separated
- extractionthe aqueous was extracted with dichloromethane (3×30 mL)
- washThe combined organics were washed with brine
- dry with materialdried over sodium sulfate
- filtrationfiltered
- concentrationconcentrated
- customPurification by flash column chromatography
Sources & evidence
- ORD record
- ord-2795ef8b55904208a3774da3e68ac2fb
- Source dataset
- uspto-grants-2014_10
- Patent number
- US08859773B2
Reaction notes
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