Preparation of bile acids and intermediates thereof
Synthetic methods for preparing deoxycholic acid and intermediates thereof are provided.
1. A method of preparing a compound of formula 1.7:
comprising
reacting a compound of formula 1.6:
with an alkylpropiolate HC≡CC(O)OR or an alkyl acrylate CH 2 ═CHC(O)OR wherein R is alkyl in the presence of a Lewis acid to form a compound of formula 1.7 wherein P is a protecting group, R is a alkyl, and the dashed line ---- is a single or double bond, to provide the compound of formula 1.7.
2. The method of claim 1 wherein the Lewis acid is EtCl 2 .
3. The method of claim 1 wherein the alkylpropiolate or alkylacrylate is methylpropriolate or methylacrylate.
4. A method of preparing a compound of formula 2.1:
comprising reacting a compound of formula 2.0
with a reducing agent to form a compound of formula 2.1 wherein P is a protecting group and R is alkyl, to provide a compound of formula 2.1.
5. The method of claim 4 wherein the reducing agent is LiAl(OtBu) 3 H.