Benzyl Chloride → 1-Benzyl-4-(2-phenylethyl)-1,2,3,6-tetrahydropyridine

Temperature

0 °C

4-(2-Phenylethyl)pyridine (8.5 g, 46 mmol) and benzyl chloride (11.64 g, 92 mmol) were refluxed in acetone for 48 h. The precipitated 1-benzyl-4-(2-phenylethyl)pyridinium chloride was filtered, washed with acetone and dried in vacuo at 50° C. to obtain 9.35 g (65%) off the white solid. 1-Benzyl-4-(2-phenylethyl)pyridinium chloride (9.0 g, 29.0 mmol) was suspended in MeOH (100 mL) and cooled to 0° C. in an ice bath. NaBH4 (4.73 g, 207.2 mmol) was added portionwise with vigorous stirring over 40 min. After cooling and stirring for an additional 1 h, the reaction mixture was concentrated under reduced pressure and partitioned between H2O (50 mL) and CH2Cl2 (50 mL). The layers were separated, and the aqueous phase was re-extracted with CH2Cl2 (50 mL). The combined CH2Cl2 extracts were dried over Na2SO4, and concentrated under reduced pressure to provide 7.1 g (91%) of 1-benzyl-4-(2-phenylethyl)-1,2,3,6-tetrahydropyridine as a pale yellow oil. 1H NMR ((CDCl3) δ2.14 (br s, 2, N--CH2 --C H2 --CH =), 2.27 (t, 2, J=8 Hz, N--C H2 --CH2 --), 2.57 (t,2, J=6 Hz, Ph--C H2 --CH2 --), 2.73 (m, 2, Ph--CH2 --C H2 --), 2.97 (br s, 2, N--C H2--CH=), 3.59 (s, 2, Ph-CH2 --N), 5.41 (m, 1, CH=C--), 7.14-7.38 (m, 10, phenyl). 1-Benzyl-4-(2-phenylethyl)-1,2,3,6-tetrahydropyridine (7.1 g, 25.6 mmol) was refluxed in 85% H3PO4 (50 mL) for 80 h. The reaction mixture was basified with 6N NH4OH and extracted with ether (2×100 mL). The ethereal extracts were dried over MgSO4 and concentrated under reduced pressure to a residue. The crude product was purified by radial flow chromatography on silica (hexane,9:acetone,1) to yield 2.3 g (32%) of 1'-benzyl-2,3-dihydrospiro[indene-1,4'-piperidine] as a straw colored liquid. 1H NMR (CDCl3) δ1.53 (br d, 2, piperidyl β-Heq.), 1.96 (dt, 2, piperidyl β-Hax),2.02 (t, 2, Ph--CH2 --C H2 --, J=6 Hz, ), 2.20 (dt, 2, piperidyl α-Hax), 2.90 (m, 4, Ph-C H2 --CH2 -- & piperidyl α-Heq), 3.59 (s, 2, benzyl), 7.14-7.40 (m, 9, phenyl).

1. filtrationThe precipitated 1-benzyl-4-(2-phenylethyl)pyridinium chloride was filtered
2. washwashed with acetone
3. customdried in vacuo at 50° C.
4. customto obtain 9.35 g (65%) off the white solid
5. temperatureAfter cooling
6. stirringstirring for an additional 1 h
7. concentrationthe reaction mixture was concentrated under reduced pressure
8. custompartitioned between H2O (50 mL) and CH2Cl2 (50 mL)
9. customThe layers were separated
10. extractionthe aqueous phase was re-extracted with CH2Cl2 (50 mL)
11. dry with materialThe combined CH2Cl2 extracts were dried over Na2SO4
12. concentrationconcentrated under reduced pressure

ORD record

ord-ee8b061ad0e44f9ba7d5fd8dc52e75f9

Source dataset

uspto-grants-1996_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05554752