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

HRID 718434Notes

Reaction equation

HRID 718434 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:44])=[N:14][C:15]([CH3:43])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=3)=[CH:28][CH:27]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[Li+].[OH-]>CCO.O>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:44])=[N:14][C:15]([CH3:43])=[C:16]([C:26]2[CH:27]=[CH:28][C:29]([O:32][CH2:33][CH2:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=3)=[CH:30][CH:31]=2)[C:17]=1[N:18]1[CH2:23][CH2:22][C:21]([CH3:25])([CH3:24])[CH2:20][CH2:19]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118314213(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(3-(4-fluorophenyl)propoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307829(2S)-2-tert-butoxy-2-[4-(4,4-dimethyl-1-piperidyl)-5-[4-[3-(4-fluorophenyl)propoxy]phenyl]-2,6-dimethyl-3-pyridyl]acetic acidYield 86.3%

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

A mixture of (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(3-(4-fluorophenyl)propoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.031 g, 0.051 mmol) and LiOH (0.012 g, 0.513 mmol) in 9:1 EtOH/H2O (2 mL) was refluxed for 4 h. Then, cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(3-(4-fluorophenyl)propoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid (0.0254 g, 0.044 mmol, 86% yield) as solid. 1H NMR (500 MHz, CDCl3) δ 7.18-7.22 (m, 2H), 7.13-7.17 (m, 1H), 7.04-7.08 (m, 1H), 6.95-7.03 (m, 4H), 5.95 (br. s., 1H), 3.98-4.07 (m, 2H), 3.43-3.78 (m, 1H), 2.87-3.06 (m, 1H), 2.84 (t, J=7.7 Hz, 2H), 2.67 (s, 3H), 2.36 (br. s., 1H), 2.24 (s, 3H), 2.10-2.18 (m, 2H), 1.93-2.09 (m, 1H), 1.48-1.68 (m, 1H), 1.28-1.40 (m, 2H), 1.25 (s, 9H), 1.10-1.22 (m, 1H), 0.88 (br.s., 3H), 0.69 (br.s., 3H). LCMS (M+H)=577.3.

Workup

  1. temperaturewas refluxed for 4 h
  2. temperatureThen, cooled
  3. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-d9c95a3c02ed4f91a06ceb258ddff81c
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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