Q78E
Question
Tamoxifen is a drug used in the treatment of breast cancer. How would you prepare tamoxifen from benzene, the following ketone, and any other reagents needed?
Step-by-Step Solution
VerifiedIn this case, however the tetrasubstituted double bond can’t be formed by a Wittig reaction because of steric hindrance. The coupling step is achieved by a Grignard reaction between the illustrated ketone and Grignard reagent, followed by dehydration. The Grignard reagent is synthesized from 1-phenyl-1-propanol, which can be prepared from benzene by either of two routes which acts as a starting material for the synthesis of Tamoxifen.
The Wittig reaction or Wittig olefination is a chemical reaction of an aldehyde or ketone with a triphenyl phosphonium ylide called a Wittig reagent. Wittig reactions are most commonly used to convert aldehydes and ketones to alkenes. The geometry of the resulting alkene depend upon the reactivity of the ylide. Ylides can be synthesized from an alky halide and trialkyl phosphine.
Wittig reaction
When you see a product that contain a double bond, and you also know that one of the starting material is ketone, it is obvious to use a Wittig reaction for its synthesis.
In this case, however the tetrasubstituted double bond can’t be formed by a Wittig reaction because of steric hindrance. The coupling step is achieved by a Grignard reaction between the illustrated ketone and Grignard reagent, followed by dehydration. The Grignard reagent is synthesized from 1-phenyl-1-propanol, which can be prepared from benzene by either of two routes as shown below:
Preparation of 1-phenyl-1-propanol
Conversion of 1-phenyl-1-propanol into tamoxifen is a multistep process. The synthesis of tamoxifen is shown below:
Tamoxifen
Synthesis of tamoxifen