A practical asymmetric synthesis of (R)-fluoxetine and its major metabolite (R)-norfluoxetine

doi:10.1016/S0040-4039(01)01877-9

Tetrahedron Letters

Volume 42, Issue 51, 17 December 2001, Pages 8919-8921

https://doi.org/10.1016/S0040-4039(01)01877-9 Get rights and content

Abstract

A convenient and chromatography-free synthesis for the enantiomers of fluoxetine and norfluoxetine is described. The synthesis relied on the use of the CBS reduction, and Hofman rearrangement to establish the key common intermediate 5, and enrichment of optical purity of the final product by crystallization as the tartrate salt.

A convenient and chromatography-free synthesis for the enantiomers of fluoxetine and norfluoxetine is described.

References (27)

H.E. Master et al.
Tetrahedron Lett.
(1996)
R. Chenevert et al.
Tetrahedron
(1992)
M.P. Schneider et al.
Tetrahedron: Asymmetry
(1992)
A. Kumar et al.
Indian J. Chem.
(1992)
R. Chenevert et al.
Chem. Lett.
(1991)
S. Sakuraba et al.
Synlett
(1991)
94% e.e. was reported by Corey, see: (a) Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C.-P.; Singh, V. K. J. Am....
D.H.R. Barton
J. Chem. Soc., Chem. Commun.
(1965)
Murphy, D. L.; Mueller, E. A.; Garrick, N. A.; Aulakh, C. S. J. Clin. Psychiatry 1986, 47, (4, Suppl.), 9; DE 2 500...

D.W. Robertson et al.

J. Med. Chem.

(1988)

D.W. Robertson et al.

J. Med. Chem.

(1988)

M. Quiros et al.

Tetrahedron: Asymmetry

(1997)

Cited by (106)

Enantioselective synthesis of structurally diverse aryl γ-/δ- lactones using an engineered carbonyl reductase
2023, Biochemical Engineering Journal
Optically pure aryl γ-/δ-lactones are valuable building blocks in the organic synthesis of natural products and pharmaceutical compounds. The asymmetric reduction of aryl keto acids or esters using carbonyl reductase provides a green and atom-economic synthetic route to these molecules. However, this method is still challenging due to the substantial steric hindrance of substrates, which has limited its practical application. Herein, we report the engineering of a carbonyl reductase SmCR_V4, which showed excellent enantioselectivity (99% (S)) for methyl 3-benzoyl propionate (1a), to obtain the mutant SmCR_W6 by directed evolution. The specific activity and catalytic efficiency of SmCR_W6 towards 1a were 4.9-fold and 3.2-fold higher than those of the parent SmCR_V4, respectively. The mutant SmCR_W6 showed a broad substrate scope (26 examples) with improvement in specific activity and enantioselectivity for most substrates. Finally, 7 chiral aryl lactones and 10 aliphatic lactones were prepared using lyophilized enzyme powder. In scaled-up synthesis, three aryl γ-/δ-lactones were prepared with > 97% conversions, 76 − 88% yields and ee up to > 99%, and the highest space-time yield (STY) of 28.2 g L⁻¹ h⁻¹ reported so far for (S)-γ-phenyl-γ-butyrolactone was obtained through biocatalysis.
Cu(II)-catalyzed regioselective ring-opening of N-tosylazetidines with phenols
2023, Tetrahedron
Highly efficient and enantioselective synthesis of chiral lactones via Ir-catalysed asymmetric hydrogenation of ketoesters
2022, Chemical Communications
Owing to the biological significance and great synthetic value of chiral lactones and their derivatives, increasing attention has been paid to developing effective synthetic methods for chiral lactones. We herein report an efficient asymmetric hydrogenation of benzo-fused ketoesters, γ-ketoesters and biaryl-bridged ketoesters catalyzed by chiral iridium complexes bearing ferrocene-based chiral ligands, furnishing a series of chiral lactones in superb yields and excellent enantioselectivities (up to 99% yields and up to 99% ee).
Ni-Catalyzed Asymmetric Hydrogenation of Aromatic Ketoacids for the Synthesis of Chiral Lactones
2022, Organic Letters
A highly efficient Ni-catalyzed asymmetric hydrogenation of aromatic γ- and δ-ketoacids has been developed, affording a series of γ- and δ-aryl lactones in high yields and excellent enantioselectivities (≤98% ee). The hydrogenation could occur smoothly on a gram scale with 0.05 mol % catalyst loading (S/C = 2000). This protocol provides an efficient and practical approach for accessing chiral lactones with important potential applications in organic synthesis and the pharmaceutical industry.
Intermolecular [4 + 2] process of N-acyliminium ions with simple olefins for construction of functional substituted-1,3-oxazinan-2-ones
2021, Chinese Chemical Letters
An efficient approach to functionalized 4,6-disubstituted-and 4,6,6-trisubstituted-1,3-oxazinan-2-ones skeleton has been developed through the reaction of semicyclic N,O-acetals 4a and 4b with 1,1-disubstituted ethylenes 5 or 8. As a result of such a [4 + 2] cycloaddition process, 4,6,6-trisubstituted-1,3-oxazinan-2-ones 6aa, 6af-6au, 7ba, 7bf-7bw and 6,6-spiro containing 1,3-oxazinan-2-ones 9ad, 9ae, 10ba-10bg were obtained in 36%-96% yields and with moderate to excellent diastereoselectivities. In addition, the synthesis of (±)-norallosedamine 12 could be conveniently achieved from the cycloadduct 7bf.
Stereochemistry: A Three-Dimensional Insight
2021, Stereochemistry: A Three-Dimensional Insight

View all citing articles on Scopus

^☆: This paper is dedicated to Professor Carl R. Johnson on the occasion of his retirement.

View full text

A practical asymmetric synthesis of (R)-fluoxetine and its major metabolite (R)-norfluoxetine☆

Abstract

Tetrahedron Lett.

Tetrahedron

Tetrahedron: Asymmetry

Indian J. Chem.

Chem. Lett.

Synlett

J. Chem. Soc., Chem. Commun.

J. Med. Chem.

J. Med. Chem.

Tetrahedron: Asymmetry