p-Toluenesulfonic acid → HCID 21187462, compound

Temperature

80 °C

A 500-mL three-neck round bottom flask was equipped with an overhead mechanical paddle stirrer, thermocouple with N2-inlet, and reflux condenser that was vented to the atmosphere. The reactor was charged with the product of Example 9 (45.68 g, 188.5 mmol), p-toluenesulfonic acid monohydrate (46.67 g, 2453 mmol, 1.3 equiv) and isopropanol (179.2 g). The mixture was warmed to 80±10° C. After 45 minutes, the reaction solution was allowed to slowly cool; at about 78° C. the p-toluenesulfonate salt of the title compound began to precipitate from the reaction mixture. When the mixture had reached 70° C., heptane (40.2 g) was added to the mixture, which was then stirred for about 30 minutes. The mixture was then allowed to cool to ambient temperature over about 3 hours. The suspension was filtered and the reactor and cake were rinsed with a mixture of isopropanol (90.2 g) and heptane (78.7 g). The cake was dried under vacuum (˜100 mmHg w/N2 bleed) at a temperature of about 55-60° C. to give the p-toluenesulfonate salt of the title compound 1H NMR (400 MHz, DMSO-d6) δ ppm 1.11 (s, 3H) 1.39-1.55 (m, 2H) 2.08 (d, J=14.55 Hz, 2H) 2.28 (s, 3H) 276-2.89 (m, 2H) 3.07-3.19 (m, 2H) 7.04 (s, 1H) 7.09-7.14 (m, 2H) 7.33 (s, 1H) 7.45-7.51 (m, 2H) 8.30 (s, 2H).

1. customA 500-mL three-neck round bottom flask was equipped with an overhead mechanical paddle stirrer
2. temperaturethermocouple with N2-inlet, and reflux condenser that
3. temperatureto slowly cool
4. customat about 78° C.

ORD record

ord-09dcc5e8f0fb43828bc70e95442083cf

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260411B2