Hydrochloric Acid → HCID 178520200, compound

To a stirred suspension of KX2-391 (free base, 60.00 g) in absolute EtOH (600 mL) was added 170 mL of 2.5 M HCl (in ethanol), 25 mL EtOH being added to wash down the sides of the flask. The resulting homogeneous solution was stirred at room temperature (20 min) and then evaporated to near dryness (to frothing). After chasing with EtOH (2×150 mL), the residue was taken up again in EtOH (150 mL) and then was followed by the slow addition of heptane until the mixture appeared saturated (33 mL required for cloudiness to remain). After sitting overnight, two layers had formed. After adding additional heptane (250 mL) crystallization still could not be induced and so the reaction mixture was concentrated to a volume of ˜200 mL at which time the mixture was homogeneous. This thick homogeneous solution was added dropwise to very rapidly stirred (mechanical) EtOAc (2 L). After the addition was complete, a 25 mL EtOH rinse of the original flask and addition funnel was added to the rapidly stirred mixture. The rapid stirring was continued for another ˜1 h and then the mixture was filtered and the solid (partly gummy) was washed with EtOAc (300 mL) and then heptane. As soon as the heptane wash began, the solid got much gummier. The fitted Buchner funnel and its contents were covered (paper towel/rubber band) and immediately placed in the vacuum oven. After overnight vacuum at ˜45° C., the vacuum was released under nitrogen, and the Buchner funnel containing the product (foamy solid) was immediately placed in a zip-lock back and then, under nitrogen (glove bag), transferred to a bottle and the foamy solid broken up (spatula) to a powder. A second night under high vacuum (˜45° C.) resulted in only 1.3 g of additional weight loss. Constant weight was essentially attained with the third night of high vacuum (˜45° C.) where only 0.2 g of weight was lost. The final weight of material was 68.05 g (yield of 97%), containing 0.29 eq (4.8% w/w) of EtOAc, 0.035 eq (0.3% w/w) EtOH, and 0.03 eq (0.6% w/w) heptane. The purity was 99.6%.

1. additionadded
2. washto wash down the sides of the flask
3. customevaporated
4. additionwas followed by the slow addition of heptane until the mixture
5. waitAfter sitting overnight
6. customtwo layers had formed
7. additionAfter adding additional
8. customheptane (250 mL) crystallization still could not
9. concentrationso the reaction mixture was concentrated to a volume of ˜200 mL at which time the mixture
10. additionThis thick homogeneous solution was added dropwise
11. stirringto very rapidly stirred (mechanical) EtOAc (2 L)
12. additionAfter the addition
13. washa 25 mL EtOH rinse of the original flask and addition funnel
14. additionwas added to the rapidly stirred mixture
15. stirringThe rapid stirring
16. waitwas continued for another ˜1 h
17. filtrationthe mixture was filtered
18. washthe solid (partly gummy) was washed with EtOAc (300 mL)
19. washAs soon as the heptane wash
20. waitAfter overnight vacuum at ˜45° C.
21. additionthe Buchner funnel containing the product (foamy solid)
22. customA second night under high vacuum (˜45° C.) resulted in only 1.3 g of additional weight loss
23. customwas essentially attained with the third night of high vacuum (˜45° C.) where only 0.2 g of weight

ORD record

ord-4e1e806db0c34bf285c2bb97d91eb538

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08901297B2