反应详情

温度

67 °C

KOH liquor (1.04 eq. of 50.4 wt %) was added to a stirred, nitrogen sparged solution of 3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid (1 eq.) in undried 1-propanol (4.87 vol.). At the end of the addition, water (0.33 vol.) and toluene (3.43 vol.) were separately added to the resulting slurry. The jacket temperature was raised to 67° C. before being subjected to the following cooling profile: 67° C. to 64° C. over 3 h, 64 to 57° C. over 3 h, 57 to 45° C. over 3 h, and 45 to 20° C. over 3 h. 6 h after the end of this ramp, the jacket temperature was lowered to 0° C. over 3 h, the jacket was foil wrapped and desupersaturation was allowed to complete overnight (>6 h). The slurry was isolated by filtration through an 11 micron filter paper. The cake was sequentially washed twice with an equal weight of an ice-cold solution of toluene (41.79 wt %) in 1-propanol. The cake was dried in a 40° C. house vacuum oven to give 3-hydroxy-5-[(1S)-2-methoxy-1-methylethoxy]benzoic acid potassium salt as tri-hydrate in a typical yield of 93% of theoretical yield.

1. additionwere separately added to the resulting slurry
2. temperaturefollowing cooling profile
3. wait64 to 57° C. over 3 h
4. wait57 to 45° C. over 3 h
5. wait45 to 20° C. over 3 h
6. wait6 h after the end of this ramp, the jacket temperature was lowered to 0° C. over 3 h
7. waitdesupersaturation was allowed to complete overnight
8. custom(>6 h)
9. customThe slurry was isolated by filtration through an 11 micron
10. filtrationfilter paper
11. washThe cake was sequentially washed twice with an equal weight of an ice-cold solution of toluene (41.79 wt %) in 1-propanol
12. customThe cake was dried in a 40° C. house vacuum oven