4-Methoxybenzaldehyde → HCID 86687419, compound

To a solution of 5-fluorothiazol-2-amine (15.0 g, 127 mmol) and 4-methoxybenzaldehyde (17.3 g, 127 mmol, Spectrochem) in dichloromethane (1.0 L) was added TiCl(O-iPr)3 (66.1 g, 254 mmol, Aldrich). The mixture was stirred at room temperature for 3 h. The reaction mixture was cooled to 0° C. and NaBH(OAc)3 (108 g, 508 mmol) was added in portions and stirred at room temperature for 16 h. The reaction mixture (in portions of 200 mL) was quenched with saturated NaHCO3 solution (100 mL) and extracted with dichloromethane (2×500 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude material which was further purified by column chromatography (silica gel 100 to 200 mesh and 50 to 100% dichloromethane in hexanes) to obtain 5-fluoro-N-(4-methoxybenzyl)thiazol-2-amine (20.0 g, 45%) as brown solid. 1H NMR (400 MHz, DMSO) δ 7.84 (t, J=5.7 Hz, 1H), 7.37-7.13 (m, 2H), 6.89 (dd, J=6.4, 2.2 Hz, 2H), 6.77 (d, J=2.4 Hz, 1H), 4.28 (d, J=5.6 Hz, 2H), 3.73 (s, 3H). m/z (ESI) 239.0 (M+H)+.

1. temperatureThe reaction mixture was cooled to 0° C.
2. stirringstirred at room temperature for 16 h
3. customThe reaction mixture (in portions of 200 mL) was quenched with saturated NaHCO3 solution (100 mL)
4. extractionextracted with dichloromethane (2×500 mL)
5. dry with materialThe combined organic layer was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto obtain the crude material which
9. customwas further purified by column chromatography (silica gel 100 to 200 mesh and 50 to 100% dichloromethane in hexanes)

ORD record

ord-d86bcc565d44411a88e3bb19afee8b2e

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012443B2