Processes of producing volixibat and analogs thereof

A process of preparing a compound of Formula (I),

• or a pharmaceutically acceptable salt, hydrate, or solvate thereof, wherein:
• each R0 is independently halo, —OH, —SH, —CN, —N3, —OH, —SH, —NH2, —COOH, —O—R00, —NHR00, —NR00R00, —S—R00, —OC(O)—R00, —(C1-6)alkylene-OH, —(C1-6)alkylene-SH, —(C1-6)alkylene-NH2, wherein each R00 is independently (C1-6)alkyl;
• one of R1 and R1a is an optionally substituted (C1-6)alkylene-OSO3H or —C(O)H and the other of R1 and R1a is H, (C1-6)alkyl, NH2, NH(C1-6)alkyl, or N((C1-6)alkyl)2;
• one of R2 and R2a is an optionally substituted (C1-6)alkylene-OH, OH, or OSO3H, and the other of R2 and R2a is H, (C1-6)alkyl, NH2, NH(C1-6)alkyl, or N((C1-6)alkyl)2;
• one of R3 and R3a is an optionally substituted (C1-6)alkylene-O—R3P or —O—R3P, wherein R3P is a first alcohol protecting group, and the other of R3 and R3a is H, (C1-6)alkyl, NH2, NH(C1-6)alkyl, or N((C1-6)alkyl)2;
• one of R4 and R4a is an optionally substituted (C1-6)alkylene-OH, OH, or OSO3H, and the other of R4 and R4a is H, (C1-6)alkyl, NH2, NH(C1-6)alkyl, or N((C1-6)alkyl)2;
• each of R11 and R22 is independently an optionally substituted (C1-6)alkyl;
• n is an integer of 0-4;
• R6 is H or OH;
• the process comprising:
• contacting the compound of Formula (I-26),
• or a pharmaceutically acceptable hydrate or solvate thereof, wherein:
• R0, R11, R22, R3, R3a, R6, and n are defined above;
• one of R20a and R20b is an optionally substituted (C1-6)alkylene-O—R2P, O—R2P, or OSO3−(pyridine)+, wherein R2P is a second alcohol protecting group, and the other of R20a and R20b is H, (C1-6)alkyl, NH2, NH(C1-6)alkyl, or N((C1-6)alkyl)2;
• one of R40a and R40b is an optionally substituted (C1-6)alkylene-O—R3P, O—R3P, or OSO3−(pyridine)+, wherein R3P is a third alcohol protecting group, and the other of R40a and R40b is H, (C1-6)alkyl, NH2, NH(C1-6)alkyl, or N((C1-6)alkyl)2;
• one of R10e and R10f is C(O)H or an optionally substituted (C1-6)alkylene-OSO3−(pyridine)+ and the other of R10e and R10f is H, (C1-6)alkyl, NH2, NH(C1-6)alkyl, or N((C1-6)alkyl)2;
• with a base in an organic solvent comprising dichloromethane to produce a compound of Formula (I).