Iodine → HCID 13638849, compound

Magnesium turnings (4.04 g, 168 mmol) are introduced into diethyl ether abs. (10 ml), and the formation of the Grignard reagent is started with a crystal of iodine and 4-chlorobenzyl chloride (2.2 ml, 2.7 g, 16.8 mmol). The remaining amount of 4-chlorobenzyl chloride (19 ml, 24 g, 148.7 mmol), dissolved in diethyl ether abs. (150 ml), is added dropwise (45 min) such that the mixture boils vigorously. After addition is complete, the mixture is refluxed by heating for a further 1.5 h. A solution of 4-chlorobutyronitrile (16.6 g, 160 mmol) in diethyl ether abs. (150 ml) is added dropwise to the solution of the 4-chlorobenzyl Grignard reagent prepared in this way (45 min), the mixture is stirred for a further 45 min after the addition, toluene abs. (200 ml) is added and diethyl ether is distilled off over a bridge until a temperature of 95° C. is reached in the bottom (2.5 h). The mixture is cooled in an ice bath and dil. HCl (10%) is added at 25-30° C. until a pH of 2-3 is reached in the depositing aqueous phase. The toluene/ether phase is separated and extracted 3 times with HCl (10%, 150 ml). The collected HCl phase is washed again with toluene (100 ml) and then rendered alkaline (pH 9-10) with NaOH (32%). The depositing oily pyrroline phase is taken up in diethyl ether (300 ml), dried over K2CO3 and concentrated. The concentrated ether phase (to 50%-55% product content) is used without further purification.

1. addition(150 ml), is added dropwise (45 min) such that the mixture
2. additionAfter addition
3. temperaturethe mixture is refluxed
4. temperatureby heating for a further 1.5 h
5. customprepared in this way (45 min)
6. addition(200 ml) is added
7. distillationdiethyl ether is distilled off over a bridge until a temperature of 95° C.
8. customis reached in the bottom (2.5 h)
9. temperatureThe mixture is cooled in an ice bath
10. additiondil. HCl (10%) is added at 25-30° C. until a pH of 2-3
11. customThe toluene/ether phase is separated
12. extractionextracted 3 times with HCl (10%, 150 ml)
13. washThe collected HCl phase is washed again with toluene (100 ml)
14. dry with materialdried over K2CO3
15. concentrationconcentrated
16. customThe concentrated ether phase (to 50%-55% product content) is used without further purification

ORD record

ord-4b387dd737604c8bbfc28cb0448ada05

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06936632B2