1,4-Dioxane hydrochloride → 2-((3R)-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetic acid

HRID 1948498Notes

Reaction equation

HRID 1948498 reaction equation
[Si]([O:8][C@@H:9]([C:23]1[CH:28]=[CH:27][C:26]([C:29]2[N:33]=[C:32]([C:34]3[O:38][N:37]=[C:36]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[C:35]=3[C:45]([F:48])([F:47])[F:46])[O:31][N:30]=2)=[CH:25][CH:24]=1)[CH2:10][N:11]1[CH2:16][CH2:15][CH2:14][C@H:13]([CH2:17][C:18]([O:20]CC)=[O:19])[CH2:12]1)(C(C)(C)C)(C)C.Cl.O1CCOCC1>>[OH:8][CH:9]([C:23]1[CH:24]=[CH:25][C:26]([C:29]2[N:33]=[C:32]([C:34]3[O:38][N:37]=[C:36]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[C:35]=3[C:45]([F:48])([F:47])[F:46])[O:31][N:30]=2)=[CH:27][CH:28]=1)[CH2:10][N:11]1[CH2:16][CH2:15][CH2:14][C@H:13]([CH2:17][C:18]([OH:20])=[O:19])[CH2:12]1

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 58374082Ethyl 2-((R)-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetate

Product 1

HCID 669554722-((3R)-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetic acidYield 99.2%

Procedure

Ethyl 2-((R)-1-((S)-2-(tert-butyldimethylsilyloxy)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetate (840 mg, 1.227 mmol) was heated in 1:1 6N HCl/dioxane at 50° C. overnight. The product was concentrated in vacuo and freeze dried from MeCN/water to yield 660 mg of 2-((3R)-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidin-3-yl)acetic acid. Characterization of product by 1H NMR and chiral HPLC matched Example 18 prepared in previous synthesis.

Workup

  1. concentrationThe product was concentrated in vacuo and freeze
  2. dry with materialdried from MeCN/water

Sources & evidence

ORD record
ord-1b1927f4f70c488aa4adb57f799e613d
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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