Hydrochloric Acid → HCID 17973432, compound

Temperature

-50 °C

A nitrogen atmosphere was applied to a reaction vessel and 50 ml of dry tetrahydrofuran is added. The solvent was cooled to less than −40° C. and 32 mmoles of lithium diisopropylamide in tetrahydrofuranne-heptane was added (16 ml of a 2 M solution). A solution of 6.97 g (30 mmoles) of α-[3-(dimethylamino)propyl]-3-methoxybenzeneacetonitrile in 30 ml of tetrahydrofuran was added at less than −20° C. and left at this temperature for 30 min. The mixture was then cooled to −50° C. and a solution of 6.62 g (33 mmoles) of diethyl isopropylidenemalonate in 30 ml of tetrahydrofuran was added to the reaction mixture at a rate such that the temperature did not exceed −50° C. The mixture was stirred at −50° C. for 30 min and the cold reaction mixture added to a stirred solution of 30 ml of aqueous hydrochloric acid (36% w/w) in 100 ml of water cooled to 10° C. The mixture was extracted twice with toluene and the toluene phase is back extracted with a solution of 2 ml of hydrochloric acid (36% w/w) in 8 ml of water. The aqueous acidic extract was combined with the aqueous acidic phase from above and extracted twice with 50 ml portions of methylene chloride. The combined methylene chloride extracts were washed with water and the methylene chloride phase filtered and concentrated to low volume by distillation at atmospheric pressure. A 100 ml portion of ethyl acetate was added and the resulting slurry cooled to 5–10° C. The resulting solid was collected by filtration, washed with ethyl acetate and dried at 50° C. to give 10.1 g of white powder.

1. customA nitrogen atmosphere was applied to a reaction vessel
2. temperatureThe solvent was cooled to less than −40° C.
3. customdid not exceed −50° C
4. customthe cold reaction mixture
5. temperaturecooled to 10° C
6. extractionThe mixture was extracted twice with toluene
7. extractionthe toluene phase is back extracted with a solution of 2 ml of hydrochloric acid (36% w/w) in 8 ml of water
8. extractionThe aqueous acidic extract
9. extractionextracted twice with 50 ml portions of methylene chloride
10. washThe combined methylene chloride extracts were washed with water
11. filtrationthe methylene chloride phase filtered
12. concentrationconcentrated to low volume by distillation at atmospheric pressure
13. additionA 100 ml portion of ethyl acetate was added
14. temperaturethe resulting slurry cooled to 5–10° C
15. filtrationThe resulting solid was collected by filtration
16. washwashed with ethyl acetate
17. customdried at 50° C.

ORD record

ord-a3b66b85c8214a8b9aa950e080e14956

Source dataset

uspto-grants-2007_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07189742B2