Reaktionsgleichung
[NH2:1][C:2]1[C:10]([Br:11])=[C:9]([F:12])[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].[CH3:13][NH2:14].CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O.C1COCC1>CCOC(C)=O>[NH2:1][C:2]1[C:10]([Br:11])=[C:9]([F:12])[CH:8]=[CH:7][C:3]=1[C:4]([NH:14][CH3:13])=[O:5]Komponenten
Versuchsvorschrift
To a slurry of 2-amino-3-bromo-4-fluorobenzoic acid (719; 0.690 g, 2.95 mmol) in 5 mL EtOAc was added methanamine (2.0 M in THF; Aldrich, St. Louis, Mo.; 5.90 mL, 11.79 mmol) to give a solution. 1-propanephosphonic acid cyclic anhydride 50 wt % in EtOAc (Matrix Scientific; 1.911 mL, 3.24 mmol) was added. The reaction became warm. The reaction was sealed and stirred rapidly at RT. After 30 min, additional methanamine 2.0 M in THF (Aldrich, St. Louis, Mo.; 5.90 mL, 11.79 mmol) was added. After 1 h, the reaction was partitioned between sat'd NaHCO3 and EtOAc. The organic layer was washed with sat'd NaHCO3 once, sat'd NaCl once, and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give 2-amino-3-bromo-4-fluoro-N-methylbenzamide (0.57 g, 2.30 mmol, 78% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.36 (1H, d, J=3.9 Hz), 7.57 (1H, dd, J=8.8, 6.3 Hz), 6.89 (2H, br. s.), 6.57 (1H, t, J=8.6 Hz), 2.74 (3H, d, J=4.5 Hz). MS (ESI, pos. ion) m/z: 246.9/248.9 (M+1).
Aufarbeitung
- customto give a solution
- temperatureThe reaction became warm
- customThe reaction was sealed
- waitAfter 1 h
- customthe reaction was partitioned between sat'd NaHCO3 and EtOAc
- washThe organic layer was washed with sat'd NaHCO3 once
- dry with materialthe organics were dried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
Quellen und Nachweise
- ORD-Eintrag
- ord-c40cd81cc735448c95c76cf713822d0b
- Quelldatensatz
- uspto-grants-2016_07
- Patentnummer
- US09394297B2
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