Sulfate Ion → Sulfate Ion

The Compound A freebase (25 g, 38.3 mmol) was dissolved in absolute ethanol (150 mL) at 22° C. The batch was filtered through a 5 μm filter and the filter flushed with absolute ethanol (50 mL). A solution of sulfuric acid/ethanol was prepared at <5° C. by charging concentrated sulfuric acid (3.91 g, 38.3 mmol) into a cooled solution (<5° C.) of absolute ethanol (50 mL) at such a rate that the temperature remained <5° C. A portion of the acid solution (10 mL, 20 vol %) was charged into the Compound A batch solution at 22° C. The Compound A batch may or may not be seeded at this point with Compound A.sulfate.ethanolate (500 mg) at 22° C. Ideally, the Compound A batch was seeded, as seeding relieves supersaturation during crystallization. The slurry was aged at 20-25° C. for 30 minutes. The remainder of the acid solution was charged into the batch via canula over 60 minutes. The batch temperature remained 20-25° C. during the addition (note: the acid solution was held at <°5 C.) The final batch slurry was aged at 20-25° C. for 60 minutes and filtered. The cake was washed with absolute ethanol (2×25 mL) and dried in vacuo (25″ Hg, 20 C.) for 18 hours with a nitrogen bleed to afford the Compound A sulfate. The sulfate salt is characterized by differential scanning calorimetry (DSC) curve, at a heating rate of 10° C./min in an open cup under flowing nitrogen exhibiting an endotherm with an extrapolated onset temperature of about 190° C., a peak temperature of about 193° C. and an associated heat of about 120 J/gm. Based on results of TG and TG-FTIR, the endotherm is due to the combination of the loss of the ethanol and melting with decomposition. The x-ray powder diffraction pattern is characterized by d-spacings of 11.72, 5.56, 5.20, 5.00, 4.60, 4.50, 4.40, 4.26, 4.17, 4.08, 3.90, 3.81, 3.69, 3.24 and 3.33 Å.

1. filtrationThe batch was filtered through a 5 μm
2. filtrationfilter
3. customthe filter flushed with absolute ethanol (50 mL)
4. customremained <5° C
5. customat 22° C
6. customduring crystallization
7. additionThe remainder of the acid solution was charged into the batch via canula over 60 minutes
8. additionThe batch temperature remained 20-25° C. during the addition (note
9. wait) The final batch slurry was aged at 20-25° C. for 60 minutes
10. filtrationfiltered
11. washThe cake was washed with absolute ethanol (2×25 mL)
12. customdried in vacuo (25″ Hg, 20 C
13. wait) for 18 hours with a nitrogen bleed

ORD record

ord-0e100b3c4364493b9bdbc6e2f8755f52

Source dataset

uspto-grants-2001_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06180634B2