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

HRID 718427Notes

Reaction equation

HRID 718427 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:43])=[N:14][C:15]([CH3:42])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[O:40][CH3:41])=[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]([CH3:43])=[N:14][C:15]([CH3:42])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[O:40][CH3:41])=[CH:28][CH:27]=2)[C:17]=1[N:18]1[CH2:19][CH2:20][C:21]([CH3:25])([CH3:24])[CH2:22][CH2:23]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118314208(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((2-methoxybenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307718(2S)-2-tert-butoxy-2-[4-(4,4-dimethyl-1-piperidyl)-5-[4-[(2-methoxyphenyl)methoxy]phenyl]-2,6-dimethyl-3-pyridyl]acetic acidYield 72.1%

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-((2-methoxybenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.036 g, 0.061 mmol) and LiOH (0.015 g, 0.611 mmol) in 9:1 EtOH/H2O (2 mL0 was refluxed for 3 h. Then, cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((2-methoxybenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid (0.0247 g, 0.044 mmol, 72.0% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.50 (dd, J=1.5, 7.5 Hz, 1H), 7.34 (dt, J=1.7, 7.8 Hz, 1H), 7.14-7.17 (m, 1H), 7.06-7.10 (m, 3H), 7.01 (dt, J=1.0, 7.5 Hz, 1H), 6.95 (d, J=8.2 Hz, 1H), 5.94 (br. s., 1H), 5.17-5.24 (m, 2H), 3.91 (s, 3H), 3.61 (br. s., 1H), 2.90 (br. s., 1H), 2.66 (s, 3H), 2.24 (s, 3H), 1.24 (s, 9H), 0.88 (br.s., 3H), 0.68 (br.s., 3H). 6H of piperidine were not resolved. LCMS (M+H)=561.4.

Workup

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

Sources & evidence

ORD record
ord-4096b0410d5e4c82bc426b6804d97de1
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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