Verapamil is a calcium channel blocker used for, among other things, the treatment of hypertension a — Physical Chemistry Chemistry Question
Verapamil
Verapamil is a calcium channel blocker used for, among other things, the treatment of hypertension and cardiac arrhythmia. It can be prepared from the reaction between H and M which can be synthesised according to the schemes below.
[VISUAL]
[VISUAL]
Suggest reagents for the multi-step conversion of A into the racemic acid B.
Model Answer
[VISUAL]
Reagents:
i) strong base (to make enolate) then (CH3)2CHI
ii) strong base then CH2=CHCH2Br
iii) hydroxide (to hydrolyse ester)
Suggest a reagent for the conversion of C in D.
Model Answer
[VISUAL]
Reagent:
SOCl2 or PCl5
Suggest structures for intermediates E, F, G and H.
Model Answer
[VISUAL]
Structures:
- E: Organoborane intermediate formed by hydroboration of the terminal double bond of D with R2BH.
- F: Amide formed by treating E with NH3, converting the acid chloride (COCl) to an amide (CONH2).
- G: Alcohol formed by oxidation of the organoborane group in F with H2O2.
- H: Chloro-nitrile formed by treating G with PCl5, which converts the alcohol (OH) to a chloride (Cl) and dehydrates the amide (CONH2) to a nitrile (CN).
Suggest a reagent for the conversion of I into J.
Model Answer
[VISUAL]
Reagent:
LiAlH4
Direct monomethylation of amines with MeI is generally not possible and hence amine J was converted into amine M by way of intermediates K and L. Suggest structures for K and L.
Model Answer
[VISUAL]
Structures:
- K: Imine formed by condensation of J (3,4-dimethoxyphenethylamine) with benzaldehyde (PhCHO).
- L: Iminium iodide salt formed by methylation of K with methyl iodide (MeI).
- M: Formed by subsequent hydrolysis of the iminium salt L.
How would you prepare the ester A from the nitrile I.
Model Answer
[VISUAL]
Steps:
i) acidic or basic hydrolysis (giving the carboxylic acid)
ii) MeOH, acid