反应详情

温度

16 °C

A visually clean 100 L flask equipped with a mechanical stirrer thermocouple and water chilled condenser was charged with MeOH (50 L). 2-iodo-5-methylbenzoic acid (5.85 kg, 22.32 mol) was then added while stirring. Concentrated sulfuric acid (0.595 L, 11.16 mol) was then added portion-wise which caused an increase in temperature from 17° C. to 22° C. This mixture was gradually brought to an internal temperature of 64.6° C. and aged overnight (˜18 h). The next morning the reaction had reached >98% conversion by HPLC. The flask was cooled to 16° C. by placing in an ice bath and 850 mL of 10 N NaOH (0.98 equiv.) was added slowly (over 10 minutes) while monitoring the pH. After the addition the pH was 5-6 (caution: bringing pH over 9 can result in saponification during the work-up). The solution was then concentrated to about 16 L and this suspension was transferred to a 100 L extractor. The flask was rinsed with 8 L of IPAc and 4 L of water which were also transferred to the extractor. 32 L of IPAc were added along with 10 L of 5 w % NaHCO3 and 10 L of 15 w % Brine. The layers were cut and the aqueous layers were back-extracted with 20 L of IPAc. The organic layers were then combined and washed with 10 L of 15 w % Brine. The organic layers were collected to provide B-1 (6.055 kg, 2193 mol, 98% yield) in 98.3% purity. 1H NMR (500 MHz, CDCl3, 293K, TMS): 7.84 (1 H, d, =8.07 Hz), 7.62 (1 H, d, J=2.14 Hz), 6.97 (1 H, dd, J=8.08, 2.14 Hz), 3.97-3.86 (3 H, m), 2.33 (3 H, s).

1. customA visually clean 100 L flask equipped with a mechanical stirrer thermocouple and water chilled condenser
2. temperaturean increase in temperature from 17° C. to 22° C
3. customwas gradually brought to an internal temperature of 64.6° C. and aged overnight (˜18 h)
4. customby placing in an ice bath
5. additionAfter the addition the pH was 5-6 (caution
6. customcan result in saponification during the work-up)
7. concentrationThe solution was then concentrated to about 16 L
8. washThe flask was rinsed with 8 L of IPAc and 4 L of water which
9. addition32 L of IPAc were added along with 10 L of 5 w % NaHCO3 and 10 L of 15 w % Brine
10. extractionthe aqueous layers were back-extracted with 20 L of IPAc
11. washwashed with 10 L of 15 w % Brine
12. customThe organic layers were collected
13. customto provide B-1 (6.055 kg, 2193 mol, 98% yield) in 98.3% purity