Lithium Hydroxide → (2S)-2-[5-(4-benzyloxyphenyl)-4-(4,4-dimethyl-1-piperidyl)-2,6-dimethyl-3-pyridyl]-2-tert-butoxy-acetic acid

HRID 718426Notes

Reaction equation

HRID 718426 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]([N:34]3[CH2:39][CH2:38][C:37]([CH3:41])([CH3:40])[CH2:36][CH2:35]3)=[C:17]([C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([O:26]CC)=[O:25])[C:18]([CH3:22])=[N:19][C:20]=2[CH3:21])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-]>CCO.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:16]([N:34]3[CH2:35][CH2:36][C:37]([CH3:41])([CH3:40])[CH2:38][CH2:39]3)=[C:17]([C@H:23]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:24]([OH:26])=[O:25])[C:18]([CH3:22])=[N:19][C:20]=2[CH3:21])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118314202(S)-ethyl 2-(5-(4-(benzyloxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118307814(2S)-2-[5-(4-benzyloxyphenyl)-4-(4,4-dimethyl-1-piperidyl)-2,6-dimethyl-3-pyridyl]-2-tert-butoxy-acetic acidYield 85%

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

A mixture of (S)-ethyl 2-(5-(4-(benzyloxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetate (0.0224 g, 0.040 mmol) and LiOH (9.60 mg, 0.401 mmol) in 9:1 EtOH/H2O (2 mL) was refluxed for 3 h. Then, cooled and purified by prep-HPLC to afford (S)-2-(5-(4-(benzyloxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)-2-(tert-butoxy)acetic acid (0.018 g, 0.034 mmol, 85% yield) as white solid. 1H NMR (400 MHz, CDCl3) δ 7.32-7.49 (m, 5H), 7.12-7.16 (m, 1H), 6.97-7.08 (m, 3H), 5.65 (br. s., 1H), 5.09-5.18 (m, 2H), 2.81 (s, 3H), 2.29 (s, 3H), 1.23-1.38 (m, 4H), 1.20 (s, 9H), 0.77 (br. s., 6H). 4H of piperidine were not resolved. LCMS (M+H)=531.4.

Workup

  1. temperaturewas refluxed for 3 h
  2. temperatureThen, cooled
  3. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-862993fa748644e5a7475e5c29919340
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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