Compounds and synthetic methods for the preparation of retinoid X receptor-specific retinoids

A method of making Compound 38,

• or a pharmaceutically acceptable salt thereof,
• wherein:
• Compound 38 has an enantiomeric excess of Compound A,
• of least about 98.0%;
• comprising a synthetic process of preparing an intermediate compound, wherein the intermediate compound is Formula (XIa),
• or a hydrate or a solvate thereof,
• wherein the intermediate compound has an enantiomeric excess of a compound of Formula (XI),
• or a hydrate or a solvate thereof,
• of at least about 80.0%;
• wherein the process of preparing the intermediate compound, comprises contacting a compound of Formula (XII),
• or a solvate thereof, with:
• a) CH2I2, Et2Zn, ZnI2, and an enantioselectivity inducer of Formula (XV) or its enantiomer,
• or a solvate thereof,
• such that the intermediate compound is prepared;
• or
• b) (i) an enantioselectivity inducer of Formula (XIII),
• or a solvate thereof,
• in a solution in the presence of CH2I2 and Et2Zn to form a reaction product of the compound of Formula (XII), or a solvate thereof;
• and
• (ii) subsequently, contacting the solution of step (i) with H2O2, such that the compound of Formula (XI) or a solvate thereof is prepared;
• or
• c) an enantioselectivity inducer of Formula (XIV) or its enantiomer,
• or a solvate thereof,
• in the presence of CH2I2 and dialkylzinc such that the intermediate compound is prepared,
• wherein the entire method of making Compound 38 comprises only a single synthetic step to produce the compound of Formula (XI).