Methods of producing cancer treating compounds
Provided herein are methods of making the compound of Formula I: and certain intermediates involved in such process.
1. A method of producing the compound of Formula 14
where n is an integer greater than 2, the method comprising esterify, by acid catalysis with acetyl chloride in methanol, the compound of Formula 15
to form the compound of Formula 16
react the compound of Formula 16 with Boc 2 O to form the compound of Formula 17
and
hydrolyze the compound of Formula 17 with NaOH to form the compound of Formula 14.
2. The method of claim 1 , wherein the compound of Formula 14 is Boc-12-AD (4)
3. The method of claim 1 , wherein the reaction with Boc 2 O with the compound of Formula 16 is in CH 2 Cl 2 in the presence of dimethylaminopyridine and a tertiary amine base.
4. The method of claim 3 , wherein the tertiary amine base is triethylamine.
5. The method of claim 1 , wherein the yield of the compound of Formula 14 is at least 97%.
6. A method of producing Boc-12-AD, having Formula
the method comprising esterify, by acid catalysis with acetyl chloride in methanol, 12-AD, having Formula 10
to form the compound of Formula 11
react the compound of formula 11 with Boc 2 O to form the compound of Formula 12
and
hydrolyze the compound of Formula 12 with NaOH to form the compound of Formula 4.
7. The method of claim 6 , wherein the reaction with Boc 2 O with the compound of Formula 11 is in CH 2 Cl 2 in the presence of dimethylaminopyridine and triethylamine.
8. The method of claim 1 , wherein the compound of Formula 14 comprises essentially no dimer impurities.
9. The preparation of claim 8 , wherein the compound is Boc-12-AD, having Formula 4.