Sodium Methoxide → HCID 17980129, compound

1-Bromo-4,5-difluoro-2-nitro-benzene (24 g, 100 mmol) was carefully added dropwise to a solution of sodium methoxide (1.2 eq) in MeOH. After addition was complete, the reaction was stirred at room temperature for 2.5 hours. The solvent was removed in vacuo and the residue diluted with water and extracted 2×250 mL with Et2O. The organic layers were combined, dried over MgSO4, filtered, and the solvent removed in vacuo leaving a yellow solid of 1-bromo-4-fluoro-5-methoxy-2-nitro-benzene: 1H NMR (300 MHz, CDCl3) 3.99 (s, 3H), 7.26 (m,1H) , 7.83 (d, 1H). MS(FD+): m/z 249, 251 (M+). Calculated for C7H5BrFNO3: C, 33.63; H, 2.02; N, 5.60; found: C, 33.79; H, 1.98; N, 5.62. 1-Bromo-4-fluoro-5-methoxy-2-nitro-benzene (20.5 g, 82 mmol) was hydrogenated over Pt on C (sulfided) at 60 psi (413 kPa) in THF (600 mL) for 4 hours. The reaction was filtered through celite to remove the catalyst. Removal of the solvent left a brown solid of 2-bromo-5-fluoro-4-methoxy-phenylamine which was taken on without further purification. 2-Bromo-5-fluoro-4-methoxy-phenylamine (18 g, 81.8 mmol) was dissolved in pyridine (200 mL) in a 500 mL round bottom flask equipped with a stir bar, septum, pressure equalizing dropping funnel, and nitrogen line with bubbler. The solution was cooled in an ice bath and ethyl chloroformate (1.5 eq.,122.7 mmol) was added dropwise from the dropping funnel. After addition was complete, the reaction was allowed to stir overnight gradually warming to room temperature. The pyridine was removed leaving a brown residue. This residue was taken up in Et2O/water and transferred to a separatory funnel. The water was extracted with Et2O (2×300 mL). The organic layers were combined, dried over MgSO4, filtered, concentrated in vacuo to obtain a 23.62 g (99%) of a brown solid: 1H NMR (300 MHz, CDCl3, 1.33 (t, 3H), 3.85 (s, 3H), 4.23 (q, 2H), 7.09 (d, 1H), 7.97 (bd, 1H); MS(FD+): m/z 291, 293 (M+).

1. additionAfter addition
2. customThe solvent was removed in vacuo
3. additionthe residue diluted with water
4. extractionextracted 2×250 mL with Et2O
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. customthe solvent removed in vacuo

ORD record

ord-89a8eeb6ebc040769861ea2f2b744c86

Source dataset

uspto-grants-2007_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07230011B2