Methylamine → tert-Butyl 4-(2-(methylcarbamoyl)benzofuran-4-yl)piperazine-1-carboxylate
Reaction equation
C([O:3][C:4]([C:6]1[O:7][C:8]2[CH:14]=[CH:13][CH:12]=[C:11]([N:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[C:9]=2[CH:10]=1)=O)C.[C-:28]#[N:29].[Na+].CN>>[CH3:28][NH:29][C:4]([C:6]1[O:7][C:8]2[CH:14]=[CH:13][CH:12]=[C:11]([N:15]3[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:22])[CH2:17][CH2:16]3)[C:9]=2[CH:10]=1)=[O:3]Participants
Procedure
tert-Butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate (6.17 g, 16.5 mmol) and sodium cyanide (0.081 g, 1.6 mmol) were stirred overnight at rt in methyl amine (8 M in ethanol) (62 mL, 490 mmol). The solvent was removed by rotary evaporation, the residue was dissolved in dichloromethane and transferred to a separatory funnel. The mixture was washed with 2 M sodium hydroxide and water. The organic phase was separated, dried over potassium carbonate, filtered and the solvent was removed by rotary evaporation to give the title compound. Yield: 5.8 g, 98%. The crude product was used in the subsequent step iii) without further purification. 1H NMR (500 MHz, CDCl3) δ ppm 1.51 (s, 9H) 3.06 (d, 3H) 3.15-3.23 (m, 4H) 3.61-3.70 (m, 4H) 6.59-6.66 (m, 1H) 6.71 (d, 1H) 7.13 (d, 1H) 7.29-7.35 (m, 1H) 7.51 (d, 1H).
Workup
- customThe solvent was removed by rotary evaporation
- dissolutionthe residue was dissolved in dichloromethane
- customtransferred to a separatory funnel
- washThe mixture was washed with 2 M sodium hydroxide and water
- customThe organic phase was separated
- dry with materialdried over potassium carbonate
- filtrationfiltered
- customthe solvent was removed by rotary evaporation
Sources & evidence
- ORD record
- ord-5e1997d32d1c47718f906e4eb8820625
- Source dataset
- uspto-grants-2015_04
- Patent number
- US09012457B2
Reaction notes
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