反応 #8488

反応方程式

fluoxetine

(S)-(−)3-chloro-1-phenyl-1-propanol

3-fluorophenol

diethyl azodicarboxylate

triphenylphosphine

→

product

収率 15.7%

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

収率 15.7%

溶媒

diethyl ether

THF

反応条件

後処理

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

実験手順

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.

出典