4-Fluorophenol → Ammonia

Diethyl azodicarboxylate (60.5 mL, 384 mmol) was added to an ice-cooled mixture of (S)-(−)-1-benzyl-3-pyrrolidinol (56.72 g, 320 mmol), 4-fluorophenol (39.45 g, 352 mmol) and triphenyl phosphine (100.7 g, 384 mmol) in tetrahydrofuran (500 mL) and the mixture was stirred for 18 hours, allowing the temperature to rise to ambient. The reaction mixture was then concentrated in vacuo and the residue was taken up in pentane:dichloromethane, 90:10. The resulting precipitate was filtered off and the filtrate was concentrated in vacuo. The residue was then purified by column chromatography on silica gel, eluting with dichloromethane. The appropriate fractions were evaporated under reduced pressure and a portion of the residue (5 g) was dissolved in methanol (100 mL). 10% Pd/C (0.5 g) and ammonium formate (5.8 g, 92 mmol) were added and the mixture was stirred at room temperature for 3 hours. The mixture was then filtered through Arbocel® and the filtrate was concentrated in vacuo purified by column chromatography on silica gel, eluting with dichloromethane; methanol, 0.88 ammonia, 95:5:0.5 to 90:10:1, to afford the title compound as a colourless oil. 1H NMR (400 MHz, DMSO-d6) δ: 2.03 (m, 2H), 3.10-3.29 (m, 3H), 3.36 (m, 1H), 5.01 (m, 1H), 6.96 (m, 2H), 7.08 (m, 2H).

1. temperaturecooled
2. concentrationThe reaction mixture was then concentrated in vacuo
3. filtrationThe resulting precipitate was filtered off
4. concentrationthe filtrate was concentrated in vacuo
5. customThe residue was then purified by column chromatography on silica gel
6. washeluting with dichloromethane
7. customThe appropriate fractions were evaporated under reduced pressure
8. dissolutiona portion of the residue (5 g) was dissolved in methanol (100 mL)
9. stirringthe mixture was stirred at room temperature for 3 hours
10. filtrationThe mixture was then filtered through Arbocel®
11. concentrationthe filtrate was concentrated in vacuo
12. custompurified by column chromatography on silica gel
13. washeluting with dichloromethane

ORD record

ord-0d16e6558bbb4e03bd9c7994bb2b1202

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08207198B2