Sodium Hydroxide → (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-methoxyphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid

HRID 718436Notes

Reaction equation

HRID 718436 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][C:35]3[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=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].[OH-].[Na+]>CCO>[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][C:35]3[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=3)=[CH:30][CH:31]=2)[C:17]=1[N:18]1[CH2:19][CH2:20][C:21]([CH3:24])([CH3:25])[CH2:22][CH2:23]1)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 118314221(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-methoxyphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307866(S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-methoxyphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acidYield 84.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-methoxyphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.032 g, 0.053 mmol) and 1M NaOH (0.159 ml, 0.159 mmol) in EtOH (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-(4-methoxyphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid (0.0257 g, 0.045 mmol, 84% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.27-7.23 (m, 2H), 7.14 (dd, J=8.5, 2.0 Hz, 1H), 7.09-7.04 (m, 1H), 7.01-6.96 (m, 2H), 6.93-6.88 (m, 2H), 6.00 (br. s., 1H), 4.26-4.17 (m, 2H), 3.83 (s, 3H), 3.57 (br. s., 1H), 3.10 (t, J=7.1 Hz, 2H), 2.93 (br. s., 1H), 2.64 (s, 3H), 2.34 (br. s., 1H), 2.21 (s, 3H), 2.16-2.01 (m, 1H), 1.68-1.47 (m, 2H), 1.40-1.28 (m, 2H), 1.25 (s, 9H), 0.88 (br.s., 3H), 0.68 (br. s., 3H). LCMS (M+H)=575.4.

Workup

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

Sources & evidence

ORD record
ord-254e0a5d51ec4d72963401025921ffcc
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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