Chlorotrimethylsilane → 4-(8-Phenyl-1,4-dioxaspiro[4.5]dec-8-yl)pyrrolidine hydrochloride

The aminonitrile 8-pyrrolidin-1-yl-1,4-dioxaspiro[4,5]decane-8-carbonitrile (10.0 g, 42.6 mmol), dissolved in THF (90 ml), was added under argon and with ice cooling within 15 min to a 1.82M phenyl magnesium chloride solution in THF (70 ml, 0.127 mol) and the mixture was stirred for 16 h at room temperature. The reaction mixture was processed by adding saturated ammonium chloride solution (100 ml) with ice cooling and was then extracted with diethyl ether (3×100 ml). The organic phase was extracted by shaking with water (70 ml) and saturated NaCl solution (70 ml) and concentrated to small volume. A yellow crystal paste (11.8 g) was retained which in addition to the desired product still contained the ketal 8-pyrrolidin-1-yl-1,4-dioxaspiro[4,5]decane-8-carbonitrile. The crude product was dissolved in ethyl methyl ketone (70 ml) and ClSiMe3 (8 ml, 0.063 mol) was added with ice cooling. After a reaction time of 6 h the hydrochloride 4-(8-phenyl-1,4-dioxaspiro[4,5]dec-8-yl)pyrrolidine hydrochloride was able to be isolated as a white solid in a yield of 43% (5.9 g).

1. extractionwas then extracted with diethyl ether (3×100 ml)
2. extractionThe organic phase was extracted
3. stirringby shaking with water (70 ml) and saturated NaCl solution (70 ml)
4. concentrationconcentrated to small volume
5. additionin addition to the desired product
6. dissolutionThe crude product was dissolved in ethyl methyl ketone (70 ml)
7. customAfter a reaction time of 6 h
8. customto be isolated as a white solid in a yield of 43% (5.9 g)

ORD record

ord-0281ec7aa5ca4d38968c7050b0abb862

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07960404B2