Continuous photolytic process for the preparation of vitamin d related substances

A method of making a vitamin D2 analog, the method comprising:

• a) mixing a compound represented by formula I:
• wherein R1 and R2 are identical or different and are hydrogen, hydroxyl, lower alkyl, lower fluoroalkyl, O-lower alkyl, lower alkenyl, lower fluoroalkenyl, O-lower alkenyl, O-lower acyl, O-aromatic acyl, lower cycloalkyl with the proviso that R1 and R2 cannot both be an alkenyl group, or taken together with the carbon to which they are bonded, form a C3-C8 cyclocarbon ring;
• R3 is lower alkyl, lower alkenyl, lower fluoroalkyl, lower fluoroalkenyl, O-lower alkyl, O-lower alkenyl, O-lower acyl, O-aromatic acyl or lower cycloalkyl;
• X1 is hydrogen or hydroxyl, or, taken with R3, constitutes a bond when R3 is an alkenyl group, and X2 is hydrogen or hydroxyl, or, taken with R1 or R2, constitutes a double bond, and X3 and X4 is hydrogen or tert-butyldimethylsilyl;
• and Y is a methylene group if the bond to Y is a double bond or is a methyl group or hydrogen if the bond to Y is a single bond, with a solvent to form a first mixture;
• b) combining the first mixture with a sensitizer to form a second mixture;
• c) subjecting the second mixture to a photoisomerization reaction by passing the second mixture through a continuous flow photoisomerization reactor to form a third mixture which comprises a compound of formula II:
• wherein R1 and R2 are identical or different and are hydrogen, hydroxyl, lower alkyl, lower fluoroalkyl, O-lower alkyl, lower alkenyl, lower fluoroalkenyl, O-lower alkenyl, O-lower acyl, O-aromatic acyl, lower cycloalkyl with the proviso that R1 and R2 cannot both be an alkenyl group, or taken together with the carbon to which they are bonded, form a C3-C8 cyclocarbon ring;
• R3 is lower alkyl, lower alkenyl, lower fluoroalkyl, lower fluoroalkenyl, O-lower alkyl, O-lower alkenyl, O-lower acyl, O-aromatic acyl or lower cycloalkyl;
• X1 is hydrogen or hydroxyl, or, taken with R3, constitutes a bond when R3 is an alkenyl group, and X2 is hydrogen or hydroxyl, or, taken with R1 or R2, constitutes a double bond, and X3 and X4 is hydrogen or tert-butyldimethylsilyl;
• and Y is a methylene group if the bond to Y is a double bond or is a methyl group or hydrogen if the bond to Y is a single bond;
• and
• wherein if X3 and X4 of formula II is tert-butyldimethylsilyl, then formula II is mixed with a deprotection reagent to obtain the vitamin D2 analog.