참여 물질
| 역할 | 이름 | HCID | 투입량 |
|---|
| 반응물 | Carbamate | HCID 276 | — |
| 반응물 | 1-Fluoronaphthalene | HCID 9450 | — |
| 반응물 | Phenyl chloroformate | HCID 15891 | — |
| 반응물 | 2,2,2-Trichloroethyl chloroformate | HCID 87063 | — |
| 반응물 | Potassium | HCID 5462222 | — |
| 반응물 | N,N-Dimethyl-3-((naphthalen-1-yl)oxy)-3-(thiophen-2-yl)propan-1-amine | HCID 11573192 | — |
| 촉매 | Zinc | HCID 23994 | — |
| 용매 | Formic Acid | HCID 284 | — |
| 생성물 | (+-)-Duloxetine | HCID 122252 | — |
반응 단계
Synthesis of duloxetine is described in detail in EP-A-273 658, EP-A-457 559 and EP-A-650965, starting from 2-acetylthiophene, an aminomethylation with dimethylamine and formaldehyde (Mannich reaction) is carried out in step-A. The 3-dimethylamino-1-(2-thienyl)-1-propanone formed is reduced to the corresponding alcohol 1-hydroxy-1-(2-thenyl)-3-dimethylaminopropane by means of complex hydrides in step B. The alcohol is then converted in step C with an alkali metal hydride and 1-fluoro-naphthalene, optionally in the presence of a potassium compound (cf. EP-A-650 965), to the naphthyl derivative, N,N-dimethyl-3-(1-naphthyloxy)-3-(2-thienyl) propylamine. In the final step D, the amino group is then demethylated by reaction with a chloroformic acid ester, preferably phenyl chloroformate or trichloroethyl chloroformate, optionally in the presence of a mixture of zinc and formic acid (EP-A-457 559), followed by alkaline hydrolysis of the carbamate to give N-methyl-3-(1-naphthyloxy)-3-(2-thienyl) propylamine.
출처 및 근거
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| 특허 번호 | US08362279B2 |
|---|
| 출처 데이터셋 | uspto-grants-2013_01 |
|---|
| ORD ID | ord-b9cafa576f644e00b686694d8a453cd5 |
|---|
| 출처 메모 | uspto-grants-2013_01 |
|---|
