Hydrochloric Acid → HCID 59315613, compound

Temperature

5 °C

Sodium hydride (977 mmol, 23.45 g) was suspended in tetrahydrofuran (700 mL) and cooled to 5° C. with an ice-water bath. To this cold suspension was added 1-vinyl-pyrrolidin-2-one (465 mmol, 51.7 g) over approximately 20 minutes, maintaining an internal temperature reaction temp of less than 5° C. then ethyl 2-bromobenzoate (437 mmol, 100 g) was added. After the addition was complete the reaction was stirred at 5° C. for 10 minutes then refluxed for 2 hours and allowed to cool to room temperature. To the suspension was added 5N HCl (600 mL) dropwise, maintaining reaction temperature between 25° C. and 35° C. The bulk of the tetrahydrofuran was then distilled off at a temperature of 60° C. under vacuum. The resulting solution was cooled and further 5N hydrochloric acid (600 mL) was added and the mixture was refluxed overnight. The solution was then cooled with a salt-ice bath to 5° C. and basified by the careful addition of sodium hydroxide pellets (˜250 g) maintaining an internal temperature between 10 and 15° C. When reaction mixture was at pH 13, the cooling bath was removed and temperature allowed to reach room temperature. The reaction was then extracted with methylene chloride (1 L) and the aqueous layer was extracted with further methylene chloride (2×1 L). The combined methylene chloride extracts were dried with sodium sulfate, filtered and evaporated to dryness to give 5-(2-bromophenyl)-3,4-dihydro-2H-pyrrole (92.2 g).

1. temperaturemaintaining
2. customan internal temperature reaction temp of less than 5° C.
3. additionAfter the addition
4. temperaturethen refluxed for 2 hours
5. temperatureto cool to room temperature
6. temperaturemaintaining
7. customreaction temperature between 25° C. and 35° C
8. distillationThe bulk of the tetrahydrofuran was then distilled off at a temperature of 60° C. under vacuum
9. temperatureThe resulting solution was cooled
10. additionfurther 5N hydrochloric acid (600 mL) was added
11. temperaturethe mixture was refluxed overnight
12. temperatureThe solution was then cooled with a salt-ice bath to 5° C.
13. additionbasified by the careful addition of sodium hydroxide pellets (˜250 g)
14. temperaturemaintaining an internal temperature between 10 and 15° C
15. customWhen reaction mixture
16. customthe cooling bath was removed
17. customto reach room temperature
18. extractionThe reaction was then extracted with methylene chloride (1 L)
19. extractionthe aqueous layer was extracted with further methylene chloride (2×1 L)
20. dry with materialThe combined methylene chloride extracts were dried with sodium sulfate
21. filtrationfiltered
22. customevaporated to dryness

ORD record

ord-b9daf814cde44e6bb3660b51ab51b181

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188123B2