Sodium borohydride → Obeticholic Acid

HRID 591910Notes

Reaction equation

[OH:1][C@@H:2]1[CH2:25][CH2:24][C@@:23]2([CH3:26])[C@H:4]([C@@H:5]([CH2:29][CH3:30])[C:6](=[O:28])[C@@H:7]3[C@@H:22]2[CH2:21][CH2:20][C@@:19]2([CH3:27])[C@H:8]3[CH2:9][CH2:10][C@@H:11]2[C@H:12]([CH3:18])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH2:3]1.[BH4-].[Na+]>>[CH3:30][CH2:29][C@H:5]1[C@@H:6]([OH:28])[C@@H:7]2[C@H:22]([CH2:21][CH2:20][C@:19]3([CH3:27])[C@@H:11]([C@@H:12]([CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH3:18])[CH2:10][CH2:9][C@H:8]32)[C@:23]2([CH3:26])[C@H:4]1[CH2:3][C@H:2]([OH:1])[CH2:25][CH2:24]2

Participants

Reactant 2

HCID 4311764Sodium borohydride

HCID 67102585(R)-4-((3R,5S,6R,8S,9S,10S,13R,14S,17R)-6-ethyl-3-hydroxy-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid

Product 1

HCID 447715Obeticholic Acid

Procedure

Step 6 is the reaction of 3α-hydroxy-6α-ethyl-7-keto-5β-cholan-24-oic acid (6) with NaBH4 to form crystalline obeticholic acid. In one embodiment, Step 6 is carried out at a temperature at about 85° C. to about 110° C. in a basic aqueous solution. In one embodiment, the temperature is about 90° C. to about 95° C. In one embodiment, the basic aqueous solution is an aqueous NaOH solution. In one embodiment, the basic aqueous solution is a mixture of 50% wt. NaOH solution and water. In one embodiment, the reaction mixture of compound 6 and NaBH4 was stirred for about 3 hours to about 5 hours. In another embodiment, the reaction mixture was stirred for about 4 hours.

Sources & evidence

ORD record: ord-ad276044cf4445e49d77cb5a1199f690
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238673B2

Reaction notes

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