Esterification of a diversly functionalized molecule

One of our colleagues has to perform an esterfication reaction to prepare ester derivative of a carboxylic acid function bearing compound. The compound has a secondary OH and N-Ac functions in addition to the carboxyl group. Use of oxalyl chloride was suggested by one of us to prepare the acid chloride and covert it into the ester. 

This reaction however resulted in the formation of one exclusive compound which was other than required ester. Careful investigation of 1H-NMR & MS data revealed that reaction occurred at another site too along with at the desired site.
Later, he tried the carbodiimide coupling procedure for the same reaction, this resulted in observation of two spots of almost similar intensity well separated to each other and at desired Rf value.
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Acetonide protection in presence of acid sensitive O-Protection

Acetonide protection in presence of acid sensitive O-protective group is very critical. You have to be very careful during this reaction. Usually acetonide protection has been carried out in presence of catalytic amount of p-TSA in acetone.

But when you have acid sensitive protective group such as TBDMS, TBDPS etc, donot use p-TSA more than 0.001 equivalent otherwise acid sensitive protective group does not stand any more. The best procedure is the use of 2,2'-dimethoxy propane with 0.001 equivalent p-TSA in anhydrous THF. In this procedure your acid labile protective group will be intact in excellent yield and this is the beauty of this procedure.

Reference: Organic Syntheses, Vol. 82, p. 75 (2005); Coll. Vol. 11, p.88 (2009).

Acetonide protection in presence of acid labile O-Protection

Dr RR and Dr US have performed such a reaction few times and they have interesting observations to share, I hope these observations would be useful to many new Chemists and Grad Students in Chemistry:

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