Water → HCID 22620189, compound

Temperature

-42 °C

To a stirred solution of 1-(tert-Butoxycarbonyl)-4-chloro-2-n-pentyl-1,2-dihydropyridine (4.67 g, 16.33 mmol) in 170 ml of THF at −42° C. was added n-butyllithium (7.84 mL, 19.61 mmol) dropwise via syringe. After the mixture had stirred at −42° C. for 1 h, iodomethane (3.1 mL, 48.99 mmol) was added and stirring was continued at −42° C. for 1 h and then at room temperature for 1 h. Water (50 mL) and ether (100 mL) were added, the layers were separated, the aqueous phase was extracted with ether (2×15 mL), and the combined organic extracts were washed with brine. The organic phase was dried over K2CO3 filtered through silica gel/Celite, and concentrated in vacuo to give the crude product. Purification by column chromatography with 5% EtOAc in hexanes afforded 3.6 g (74%) of the product. 1H NMR (250 MHz) d 5.62-5.59 (d, 1H), 5.31 (br s, 1H), 4.80-4.72 (q, 1H), 2.13 (s, 1H), 1.55-1.26 (m, 17H), 0.89-0.84 (t, 3H); 13C NMR (62.7 MHz) 153.0 (s), 136.9 (s), 126.5 (s), 119.3 (s), 112.2 (s), 81.4 (s), 54.1 (s), 31.6 (s), 31.5 (s), 28.1 (s), 24.2 (s), 22.4 (s), 21.9 (s), 13.9 (s) ppm. FT-IR (neat) 2927, 2855, 1706, 1634, 1391, 1128, 1087 cm−1.

1. stirringstirring
2. waitwas continued at −42° C. for 1 h
3. waitat room temperature for 1 h
4. customthe layers were separated
5. extractionthe aqueous phase was extracted with ether (2×15 mL)
6. washthe combined organic extracts were washed with brine
7. dry with materialThe organic phase was dried over K2CO3
8. filtrationfiltered through silica gel/Celite
9. concentrationconcentrated in vacuo
10. customto give the crude product
11. customPurification by column chromatography with 5% EtOAc in hexanes

ORD record

ord-a8d58687ad1b44fca59dc3df31ca290b

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08168657B2