Triethylamine → Methanesulfonic acid 2-{4-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-phenyl}-ethyl ester

Temperature

2 °C

A solution of 2-{2-[4-(2-hydroxy-ethyl)phenyl]-ethyl}-isoindole-1,3-dione (Preparation 10, 21.0 g, 71.25 mmol) in methyl ethyl ketone (315 mL) was cooled to 0° C. Triethylamine (14.9 mL, 106.87 mmol) was added followed by the dropwise addition of methane sulfonyl chloride (6.07 mL, 78.37 mmol). The reaction was stirred at 0-4° C. for 1 hour and then allowed to warm to room temperature. An aqueous solution of potassium carbonate (1M, 210 mL) was added and the mixture stirred. The organic and aqueous layers were separated and the aqueous re-extracted with methyl ethyl ketone (50 mL). The combined organic layers were concentrated to 40 mL by distillation. Tert-butyl methyl ether (300 mL) was slowly added to the hot solution causing crystallisation to occur. The mixture was allowed to cool to room temperature and then allowed to stir for 72 hours. The solid was removed by filtration and washed with tert-butyl methyl ether (3×25 mL). The solid was dried in vacuo at 45° C. for 4 hours to yield the title compound as a light brown solid, in 92% yield, 24.6 g.

1. temperatureto warm to room temperature
2. stirringthe mixture stirred
3. customThe organic and aqueous layers were separated
4. extractionthe aqueous re-extracted with methyl ethyl ketone (50 mL)
5. concentrationThe combined organic layers were concentrated to 40 mL by distillation
6. additionTert-butyl methyl ether (300 mL) was slowly added to the hot solution
7. customcrystallisation
8. temperatureto cool to room temperature
9. stirringto stir for 72 hours
10. customThe solid was removed by filtration
11. washwashed with tert-butyl methyl ether (3×25 mL)
12. customThe solid was dried in vacuo at 45° C. for 4 hours

ORD record

ord-b35c7e18de274accbe8cd5d677b2c603

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263623B2