# US 2017/0283380 A1 · Intermediate for Synthesizing Paroxetine, Method for Preparing the same, and Uses Thereof

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- Number: US 2017/0283380 A1
- Document ID: US20170283380A1
- Status: Published application
- Kind: A1
- Application number: 15/511,244
- Filed: 2015-06-15
- Published: 2017-10-05
- Earliest claimed: 2014-09-22
- Assignees: Zhejiang Jiuzhou Pharmaceutical Co., Ltd.
- Applicants: Zhejiang Jiuzhou Pharmaceutical Co., Ltd.
- Inventors: Xiaoming FENG; Yu ZHANG; Xiaohua LIU; Qian YAO; Lili LIN; Guoliang ZHU
- Web page: https://patentgrep.com/patent/US20170283380A1

## CPC

- C07D 211/88: attached in positions 2 and 6, e.g. glutarimide
- C07C 201/12: by reactions not involving the formation of nitro groups
- C07C 205/53: the carbon skeleton containing six-membered aromatic rings
- C07D 207/267: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
- C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 231/16: Halogen atoms or nitro radicals
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

A paroxetine intermediate, a method for preparing the same, and uses thereof are provided. Specifically, the method includes: reacting a compound of formula I below with a compound of formula II in the presence of air organic base under the catalysis of a complex formed from a chiral amine oxide L and a rare-earth metal compound Ln(OTf)3 to prepare a compound of formula III below: wherein R1 is alkyl, phenyl or benzyl; R2, R3, R4 are each independently C1-C6 alkyl or C6-C10 aryl; the chiral amine oxide L has the following structure: wherein n=1, 2; and R=Ph-, 2,6-Me2C6H3-, 2,6-Et2C6H3-, 2,6-iPr2C6H3-, Ph2CH—.

## Claims

### Claim 1

A compound having the structure of formula I:
wherein R2, R3 and R4 are each independently C1-C6 alkyl or C6-C10 aryl.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein the compound has the following structure:

### Claim 3

A method of preparing a compound of formula III below,
obtained by reacting a compound of formula I with a compound of formula II in the presence of an organic base under the catalysis of a complex formed from a chiral amine oxide L and a rare-earth metal compound Ln(OTf)3:
wherein R1 is alkyl, phenyl or benzyl, preferably C1-C6 alkyl, phenyl or benzyl;
R2, R3, R4 are each independently C1-C6 alkyl or C6-C10 aryl;
the chiral amine oxide L has the following structure:
wherein n=1, 2; and R=Ph-, 2,6-Me2C6H3—, 2,6-Et2C6H3—, 2,6-iPr2C6H3—, Ph2CH—; and
Ln in the rare-earth metal compound Ln(OTf)3 represents a lanthanide metal selected from La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu.

### Claim 4 (depends on 3)

The method according to claim 3, wherein the organic base is an amine.

### Claim 5 (depends on 3)

The method according to claim 3, wherein the Ln(OTf)3 is gadolinium trifluoromethanesulfonate [Gd(OTf)3], holmium trifluoromethanesulfonate [Ho(OTf)3], ytterbium trifluoromethanesulfonate [Yb(OTf)3], erbium trifluoromethanesulfonate [Er(OTf)3].

### Claim 6 (depends on 3)

The method according to claim 3, wherein the organic base is triethylamine, diisopropylethylamine, trimethylamine, tri-n-propylamine, tri-n-butylamine, dimethyl aniline, diethylaniline, dimethyl benzylamine, diethyl benzylamine, or 1,8-diazabicyclo[5.4.0]undec-7-ene.

### Claim 7 (depends on 3)

The method according to claim 3, wherein the reaction is carried out in a solvent such as pentane, hexane, heptane, dichloroethane, chloroform, toluene, ethylbenzene, isopropyl benzene, tetrahydrofuran, methyl tert-butyl ether, 2-methyltetrahydrofuran, ethyl acetate or isopropyl acetate.

### Claim 8 (depends on 1)

A method of preparing a compound of formula I,
obtained by condensing a compound of formula IV below with p-fluorocinnamic acid in the presence of a dehydrant and an organic base,
wherein R2, R3, R4 are the same as defined in claim 1.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the dehydrant is 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, 2-(7-azabenzotriazol)-N,N,N′,N′-tetramethyluronium hexafluorophosphate, dicyclohexylcarbodiimide, or benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate.

### Claim 10 (depends on 8)

The method according to claim 8, wherein the organic base is N-methylmorpholine, triethylamine, diisopropylethylamine, trimethylamine, tri-n-propylamine, tri-n-butylamine, dimethylaniline, diethylaniline, dimethyl benzylamine, diethyl benzylamine or 1,8-diazabicyclo[5.4.0]undec-7-ene.