참여 물질
| 역할 | 이름 | HCID | 투입량 |
|---|
| 반응물 | Hexamethyldisilazane | HCID 13838 | — |
| 반응물 | 4-Fluorobenzonitrile | HCID 14517 | — |
| 반응물 | Sodium amide | HCID 24533 | — |
| 반응물 | Sodium bis(trimethylsilyl)amide | HCID 2724254 | — |
| 반응물 | HCID 178509721 | HCID 178509721 | — |
| 용매 | Dimethylformamide | HCID 6228 | — |
| 용매 | Tetrahydrofuran | HCID 8028 | — |
| 용매 | Dimethylacetamide | HCID 31374 | — |
| 생성물 | Letrozole | HCID 3902 | — |
| 생성물 | 4-Fluorobenzonitrile | HCID 14517 | — |
| 생성물 | HCID 178509721 | HCID 178509721 | — |
반응 단계
Most preferably, the base is sodium bis(trimethylsilyl)amide, which may be prepared from hexamethyldisilazane and sodium amide, or purchased as a 40 percent solution in tetrahydrofuran. To avoid reaction between the 4-fluorobenzonitrile V and the sodium bis(trimethylsilyl)amide, the base is preferably added gradually to the mixture of synthons (all known procedures first generate the anion of intermediate III prior to bringing it into contact with 4-fluorobenzonitrile V). Approximately equimolar amounts of the intermediate III and 4-fluorobenzonitrile V in dimethylacetamide, dimethylformamide, or tetrahydrofuran provide a yield of about 85 percent by weight of pure letrozole after isolation and purification. As no stoichiometric excess of 4-fluorobenzonitrile V is required, any side-reactions with the base are believed to be negligible.
출처 및 근거
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| 특허 번호 | US07705159B2 |
|---|
| 출처 데이터셋 | uspto-grants-2010_04 |
|---|
| ORD ID | ord-af800d977dea40cdaf93e3d2be94c129 |
|---|
| 출처 메모 | uspto-grants-2010_04 |
|---|
