2-Methylpyrrolidine → 1-[2-(6-Bromo-naphthalen-2-yl)-ethyl]-2-methyl-pyrrolidine

Temperature

-15 °C

To a cooled solution of 2-methylpyrrolidine (2.0 mL, 20 mmol) in THF (30 mL) at −15° C. was added n-BuLi (1.6 M in hexane, 4.0 mL, 6.4 mmol) dropwise keeping the temperature below −10° C. The resulting mixture was stirred at −15° C. for 10 min. To the cooled solution was added a solution of 2-bromo-6-vinyl-naphthalene (3) (2.33 g, 10.0 mmol) in THF (30 mL) dropwise keeping the temperature below −15° C. The resulting mixture was stirred at −15° C. for 5 min. and quenched with H2O (1 mL) and then poured into 5% Na2CO3 (80 mL). To the mixture was added EtOAc (80 mL), and organic was separated, the aqueous layer was extracted with EtOAc (30 mL). The combined organic layer was washed with brine and treated with activated carbon, dried over Na2SO4 and concentrated. The residue was then further dried under high vacuum to give 2.47 g product. The crude product was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) d 7.86 (d, 1H), 7.53–7.59 (m, 3H), 7.40–7.42 (dd,1H), 7.28–7.30 (dd, 1H), 3.04–3.22 (m, 1H), 3.98–3.04 (m, 1H), 2.85–2.91 (m, 2H), 2.23–2.33 (m, 2H), 2.14 (q, 1H), 1.81–1.88 (m, 1H), 1.62–1.78 (m, 2H), 1.32–1.39 (m, 1H), 1.04 (d, 3H). 13C NMR (400 MHz, CDCl3) d 138.50, 132.75, 131.65, 129.29, 128.90, 128.76, 128.21, 126.63, 126.34, 118.72, 60.11, 55.88, 54.15, 35.78, 32.93, 21.98, 19.28. [M+H]+ at m/z 319.

1. customthe temperature below −10° C
2. customthe temperature below −15° C
3. stirringThe resulting mixture was stirred at −15° C. for 5 min.
4. customquenched with H2O (1 mL)
5. additionpoured into 5% Na2CO3 (80 mL)
6. additionTo the mixture was added EtOAc (80 mL)
7. customorganic was separated
8. extractionthe aqueous layer was extracted with EtOAc (30 mL)
9. washThe combined organic layer was washed with brine
10. additiontreated with activated carbon
11. dry with materialdried over Na2SO4
12. concentrationconcentrated
13. customThe residue was then further dried under high vacuum

ORD record

ord-72d55d7ceea945a7bc577d91ad3e9fc5

Source dataset

uspto-grants-2006_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07145005B2