Antifungal compound process

1. A process to prepare compound 1 or 1a,

or a mixture thereof, the process comprising:

(i) forming the trimethylsilyl-cyanohydrin of aryl-pyridine 1-4,

 to provide trimethylsilyl-cyanohydrin 1-5 or 1-5a,

 or a mixture thereof;

(ii) reducing trimethylsilyl-cyanohydrin 1-5 or 1-5a,

 or a mixture thereof, to provide amino-alcohol 1-6 or 1-7,

 or a mixture thereof; and

(iii) forming the tetrazole of amino-alcohol 1-6 or 1-7,

 or a mixture thereof, to provide compound 1 or 1a,

 or a mixture thereof;

wherein forming the trimethylsilyl-cyanohydrin is performed in the presence of a chiral catalyst.

2. The process of claim 1 , further comprising enriching the enantiomeric purity of amino-alcohol 1-6 or 1-7 to afford enantio-enriched amino-alcohol 1-6* or 1-7*,

3. The process of claim 1 , further comprising:

(i) combining compound 1 or 1a,

 or a mixture thereof, a sulfonic acid

 and a crystallization solvent or crystallization solvent mixture;

(ii) diluting the mixture from step (i) with a crystallization co-solvent or crystallization co-solvent mixture; and

(iii) isolating a compound of formula IX or IXa,

 or a mixture thereof;

wherein Z is aryl, substituted aryl, alkyl, or substituted alkyl.

4. The process of claim 3 , wherein Z is phenyl, p-tolyl, methyl, or ethyl.

5. The process of claim 4 , further comprising enriching the enantiomeric purity of amino-alcohol 1-6 or 1-7 to afford enantio-enriched amino-alcohol 1-6* or 1-7*,

6. The process of claim 3 , further comprising enriching the enantiomeric purity of amino-alcohol 1-6 or 1-7 to afford enantio-enriched amino-alcohol 1-6* or 1-7*,