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. an 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 10N 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 IPAc 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 E-1 (6.055 kg, 21.93 mol, 98% yield) in 98.3% purity.

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. custom(˜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. extractionthe aqueous layers were back-extracted with 20 L of IPAc
10. washwashed with 10 L of 15 w % Brine
11. customThe organic layers were collected
12. customto provide E-1 (6.055 kg, 21.93 mol, 98% yield) in 98.3% purity