Reacción #8488

Ecuación de reacción

fluoxetine

(S)-(−)3-chloro-1-phenyl-1-propanol

3-fluorophenol

diethyl azodicarboxylate

triphenylphosphine

→

product

Rendimiento 15.7%

(R)-3-(3-Fluorophenoxy)-3-phenylpropylchloride

Rendimiento 15.7%

Disolventes

diethyl ether

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe THF was subsequently evaporated under vacuum
2. 2
   Otroto afford a gel which
3. 3
   Lavadowas washed with pentane (3×50 mL)
4. 4
   FiltraciónThe pentane washings were filtered
5. 5
   Otrothe filtrate was evaporated under vacuum
6. 6
   Otroto give a clear oil
7. 7
   Lavadowashed with 1% HCl-satd
8. 8
   SecadoThe organic layer was then dried (anh. Na2SO4)
9. 9
   Filtraciónfiltered
10. 10
    Otroevaporated to dryness under vacuum
11. 11
    Otroto give an orange oil
12. 12
    OtroThe crude product was chromatographed on silica gel (25×180 mm, gravity column), elution with 40:1 hexane-EtOAc

Procedimiento

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.

Fuente