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Stage #1: With sodium chlorite In water; acetone for 0.0833333 h; Cooling with ice Stage #2: With aminosulfonic acid In water; acetone at 0℃; for 0.5 h;
To an ice-cooled solution of sodium chlorite (6.81 g, 75.68 mmol) in water (30 mL) was added a solution of 3-Chloro-2-fluoro-benzaldehyde (3 g, 18.92 mmol) in acetone (75 mL) and the reaction mixture was stirred for 5 mm. To the resulting reaction mixture was added sulphamic acid (5.50 g, 56.76 1 mmol) in one lot at 0 °C and stirring continued for 30 mm. Progress of the reaction was monitored by TLC. After completion, the reaction mixture wasdiluted with water (5 mL) and filtered. Filtrate was extracted with ethyl acetate (3 x 50 mL), combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to get 3-chloro-2-fluoro-benzoic acid (3.2 g, 97percent) as white solid. LC-MS:172.9(M-H).
With sulfuric acid; acetic acid In water at 155℃; for 5 h;
3L bottle take four reflux means of 2-fluoro-3-chlorobenzonitrile 437g, water 500g, concentrated sulfuric acid, 1248g, acetic acid 21g, slowly warmed to reflux and reflux temperature of about 155 , heat the reaction 5h, the control sample, the raw material ≤1percent, the reaction was stopped, cooled to 50 , dropping water 750g, stirred for 1h and then cooled to 10 , filtration, the filter cake with the amount of water rinsed, drained, dried was 458.5g, content ≥99percent, yield 93.5percent.
To an ice-cooled solution of sodium chlorite (6.81 g, 75.68 mmol) in water (30 mL) was added a solution of 3-Chloro-2-fluoro-benzaldehyde (3 g, 18.92 mmol) in acetone (75 mL) and the reaction mixture was stirred for 5 mm. To the resulting reaction mixture was added sulphamic acid (5.50 g, 56.76 1 mmol) in one lot at 0 C and stirring continued for 30 mm. Progress of the reaction was monitored by TLC. After completion, the reaction mixture wasdiluted with water (5 mL) and filtered. Filtrate was extracted with ethyl acetate (3 x 50 mL), combined organic layer was dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure to get 3-chloro-2-fluoro-benzoic acid (3.2 g, 97%) as white solid. LC-MS:172.9(M-H).
3-Chloro-2-fiuorobenzaldehyde (15.9 g, 0.1 mol) was dissolved in tert-butanol (60 ml), stirred and heated under N2 at 50 0C. 2M aqueous NaOH (100 ml, 0.2 mol) was warmed to 50 0C and added to the solution of the aldehyde. Aqueous hydrogen peroxide solution (H2O2, 30%, 70 ml, 0.6 mol) was added over 45 min , maintaining the temperature at 55-60 0C. The mixture was stirred and heated under N2 for a further Ih, cooled and concentrated in vacuo. The residual slurry was filtered. The filtrate was washed with toluene (2 x xx ml) and acidified to pH 1 with 5N hydrochloric acid whilst stirring vigorously. The resulting solid was collected by filtration, washed with water and dried in vacuo at 50 0C. to give 11.1 g of product, mp 179-181 0C.A sample prepared by a different route [ J.Mortier et al, Tetrahedron Lett., 36, 881- 884 (1995)] is reported to have mp 179-181 0C.
methyl 4-chloro-2-fluorobenzoate
methyl 4-chloro-2-fluorobenzoate The desired product was prepared by substituting 3-chloro-2-fluorobenzoic acid for 4-bromo-3-fluorobenzoic acid in Example 311A.
With N-iodo-succinimide; sulfuric acid at 5 - 20℃; for 16h;
1.1
Example 1; Step 1; 3-Chloro-2-fluorobenzoic acid (25.00 g, 143.21 mmol) was dissolved in concentrated sulfuric acid (100 ml), and N-iodosuccinimide (32.20 g, 143.21 mmol) was portionwise added at 5° C. or below. After the completion of addition, the mixture was stirred at the same temperature for 3 hr, and at room temperature for 13 hr. The reaction mixture was poured into ice water (about 500 ml) added with sodium sulfite (14.90 g, 143.19 mmol) and, after stirring, the precipitated solid was collected by filtration and washed with water. The obtained solid was dried under reduced pressure at 65° C. for 8 hr to give the object compound (41.02 g, yield 95%) as a pale-brown solid.1H NMR (DMSO-d6 400 MHz) (δ) ppm: 8.06 (1H, dd, J=6.1, 2.2 Hz), 8.22 (1H, dd, J=6.4, 2.2 Hz)MS (ESI): M- 299
With sulfuric acid; acetic acid; In water; at 155.0℃; for 5.0h;
3L bottle take four reflux means of <strong>[94087-40-8]2-fluoro-3-chlorobenzonitrile</strong> 437g, water 500g, concentrated sulfuric acid, 1248g, acetic acid 21g, slowly warmed to reflux and reflux temperature of about 155 , heat the reaction 5h, the control sample, the raw material ?1%, the reaction was stopped, cooled to 50 , dropping water 750g, stirred for 1h and then cooled to 10 , filtration, the filter cake with the amount of water rinsed, drained, dried was 458.5g, content ?99%, yield 93.5%.
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