Diisopropylamine → HCID 19883412, compound

Temperature

-20 °C

A cooled (-60° C.) solution of diisopropylamine (11.13 g, 0.110 mole) in anhydrous tetrahydrofuran (150 ml) under nitrogen was treated (via syringe) with 2.4N n-butyllithium/hexane (0.105 mole), warmed to -20° C., stirred for 5 minutes, then treated in portions with 4-(N-acetylamino)-5-chloro-2-methoxybenzoic acid, methyl ester (25.8 g, 0.100 mole). After 30 minutes at 25° C., the mixture was cooled (0° C.), treated dropwise with a solution of methanesulfonyl chloride (25.0 g, 0.218 mole) in anhydrous tetrahydrofuran (50 ml), and maintained at room temperature for 30 minutes and at 50° C. for one hour. The mixture was partially concentrated in vacuo and added to ice water (600 ml), and the aqueous mixture was extracted with methylene chloride (3×250 ml). The combined organic solution was dried (sodium sulfate), concentrated in vacuo, taken up in 60:40 water/ethanol (300 ml), treated with potassium hydroxide (33.6 g, 0.60 mole), and refluxed for three hours. Most of the ethanol was removed in vacuo and replaced with water, and the aqueous solution was extracted with ether (2×200 ml), then cooled in an ice bath and treated with concentrated hydrochloric acid solution (60 ml). The suspension was filtered and the solid was washed with water, air dried, and recrystallized from 95% ethanol to afford 14.60 g (52%) of the title compound as a colorless solid; mp 248°-250° C.

1. waitAfter 30 minutes at 25° C.
2. temperaturethe mixture was cooled (0° C.)
3. temperaturemaintained at room temperature for 30 minutes and at 50° C. for one hour
4. concentrationThe mixture was partially concentrated in vacuo
5. additionadded to ice water (600 ml)
6. extractionthe aqueous mixture was extracted with methylene chloride (3×250 ml)
7. dry with materialThe combined organic solution was dried (sodium sulfate)
8. concentrationconcentrated in vacuo
9. temperaturerefluxed for three hours
10. customMost of the ethanol was removed in vacuo
11. extractionthe aqueous solution was extracted with ether (2×200 ml)
12. temperaturecooled in an ice bath
13. additiontreated with concentrated hydrochloric acid solution (60 ml)
14. filtrationThe suspension was filtered
15. washthe solid was washed with water, air
16. customdried
17. customrecrystallized from 95% ethanol

ORD record

ord-221aaef677924910bf5c4406bfe94197

Source dataset

uspto-grants-1992_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05137895