Fluoxetine → (R)-3-(3-Fluorophenoxy)-3-phenylpropylchloride

Temperatur

0 °C

Following a similar procedure for the chiral synthesis of fluoxetine [Srebnik, M. et al., J. Org. Chem. 25 53(13), 2916–20 (1988), hereby incorporated by reference herein], a solution of (S)-(−)3-chloro-1-phenyl-1-propanol (4.00 g, 23.4 mmol), 3-fluorophenol (2.63 g, 23.4 mmol), and diethyl azodicarboxylate (4.00 g, 23.4 mmol) were dissolved in THF (200 mL). The mixture was cooled to 0° C. and triphenylphosphine (6.77 g, 25.8 mmol, 1.1 equiv) was added slowly over 10 min. The reaction mixture was then stirred at room temperature for 18 h. The THF was subsequently evaporated under vacuum to afford a gel which was washed with pentane (3×50 mL). The pentane washings were filtered and the filtrate was evaporated under vacuum to give a clear oil. This oil was dissolved in diethyl ether (150 mL) and washed with 1% HCl-satd. NaCl (25 mL), 0.1N NaOH-satd. NaCl (2×25 mL), and finally H2O (2×25 mL). The organic layer was then dried (anh. Na2SO4), filtered, and evaporated to dryness under vacuum to give an orange oil. The crude product was chromatographed on silica gel (25×180 mm, gravity column), elution with 40:1 hexane-EtOAc, to provide 971 mg (15.7%) of product as a colorless oil.

1. customThe THF was subsequently evaporated under vacuum
2. customto afford a gel which
3. washwas washed with pentane (3×50 mL)
4. filtrationThe pentane washings were filtered
5. customthe filtrate was evaporated under vacuum
6. customto give a clear oil
7. washwashed with 1% HCl-satd
8. dry with materialThe organic layer was then dried (anh. Na2SO4)
9. filtrationfiltered
10. customevaporated to dryness under vacuum
11. customto give an orange oil
12. customThe crude product was chromatographed on silica gel (25×180 mm, gravity column), elution with 40:1 hexane-EtOAc

ORD-Eintrag

ord-059b828bdb38424794d4aa280bc1785d

Quelldatensatz

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07087765B2