Sodium Hydroxide → (R)-4-((3R,5R,8S,9S,10R,13R,14S,17R,Z)-6-ethylidene-3-hydroxy-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid

HRID 591866

Reaction equation

[CH3:1][CH2:2][C@H:3]1[C@@H:16]([OH:17])[C@@H:15]2[C@H:10]([CH2:11][CH2:12][C@:13]3([CH3:28])[C@@H:20]([C@@H:21]([CH2:23][CH2:24][C:25]([OH:27])=[O:26])[CH3:22])[CH2:19][CH2:18][C@H:14]32)[C@:9]2([CH3:29])[C@H:4]1[CH2:5][C@H:6]([OH:30])[CH2:7][CH2:8]2.COC(=O)CC[C@H]([C@@H]1[C@]2(C)[C@H]([C@H]3[C@H](CC2)[C@]2(C)[C@@H](C[C@H](O)CC2)/C(=C/C)/C3=O)CC1)C.[OH-].[Na+]>>[OH:30][C@@H:6]1[CH2:7][CH2:8][C@@:9]2([CH3:29])[C@H:4](/[C:3](=[CH:2]/[CH3:1])/[C:16](=[O:17])[C@@H:15]3[C@@H:10]2[CH2:11][CH2:12][C@@:13]2([CH3:28])[C@H:14]3[CH2:18][CH2:19][C@@H:20]2[C@H:21]([CH3:22])[CH2:23][CH2:24][C:25]([OH:27])=[O:26])[CH2:5]1

Participants

Reactant 3

HCID 14798Sodium Hydroxide

HCID 447715Obeticholic Acid

HCID 86706182CID 86706182

Product 1

HCID 86706181(R)-4-((3R,5R,8S,9S,10R,13R,14S,17R,Z)-6-ethylidene-3-hydroxy-10,13-dimethyl-7-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)pentanoic acid

Procedure

The present invention relates to a process for preparing obeticholic acid Form 1, comprising the steps of reacting E- or E/Z-3α-hydroxy-6-ethylidene-7-keto-5β-cholan-24-oic acid methyl ester with NaOH to form E- or E/Z-3α-hydroxy-6-ethylidene-7-keto-5β-cholan-24-oic acid; reacting E- or E/Z-3α-hydroxy-6-ethylidene-7-keto-5β-cholan-24-oic acid with Pd/C and hydrogen gas to form 3α-hydroxy-6α-ethyl-7-keto-5β-cholan-24-oic acid; reacting 3α-hydroxy-6α-ethyl-7-keto-5β-cholan-24-oic acid with NaBH4 to form crystalline obeticholic acid, and converting crystalline obeticholic acid to obeticholic acid Form 1.

Sources & evidence

ORD record: ord-81b725f92e894774a10e62ad4a37a0af
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238673B2

Linked notes

Loading…