반응 #8488

반응 방정식

fluoxetine

(S)-(−)3-chloro-1-phenyl-1-propanol

3-fluorophenol

diethyl azodicarboxylate

triphenylphosphine

→

product

수율 15.7%

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

수율 15.7%

용매

diethyl ether

THF

반응 조건

후처리

1. 1
   기타The THF was subsequently evaporated under vacuum
2. 2
   기타to afford a gel which
3. 3
   세척was washed with pentane (3×50 mL)
4. 4
   여과The pentane washings were filtered
5. 5
   기타the filtrate was evaporated under vacuum
6. 6
   기타to give a clear oil
7. 7
   세척washed with 1% HCl-satd
8. 8
   건조The organic layer was then dried (anh. Na2SO4)
9. 9
   여과filtered
10. 10
    기타evaporated to dryness under vacuum
11. 11
    기타to give an orange oil
12. 12
    기타The crude product was chromatographed on silica gel (25×180 mm, gravity column), elution with 40:1 hexane-EtOAc

실험 절차

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.

출처