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

HRID 718435Notes

Reaction equation

HRID 718435 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:40])=[N:14][C:15]([CH3:39])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[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]([CH3:40])=[N:14][C:15]([CH3:39])=[C:16]([C:26]2[CH:27]=[CH:28][C:29]([O:32][CH2:33][CH2:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[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])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118314220(S)-ethyl 2-(tert-butoxy)-2-(5-(4-(3,3-dimethylbutoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307779(S)-2-(tert-butoxy)-2-(5-(4-(3,3-dimethylbutoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acidYield 83.3%

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

A mixture of (S)-ethyl 2-(tert-butoxy)-2-(5-(4-(3,3-dimethylbutoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetate (0.02 g, 0.036 mmol) and LiOH (8.66 mg, 0.362 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-(5-(4-(3,3-dimethylbutoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid (0.0158 g, 0.030 mmol, 83% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.12-7.16 (m, 1H), 7.06 (d, J=7.7 Hz, 1H), 6.96-7.00 (m, 2H), 5.92 (br. s., 1H), 4.06-4.15 (m, 2H), 3.46-3.81 (m, 1H), 2.90 (br. s., 1H), 2.69 (br. s., 3H), 2.27-2.42 (m, 1H), 2.25 (s, 3H), 1.95-2.17 (m, 1H), 1.79 (t, J=7.3 Hz, 2H), 1.50-1.64 (m, 1H), 1.27-1.40 (m, 3H), 1.25 (s, 9H), 1.04 (s, 9H), 0.81 (br.s., 6H). LCMS (M+H)=525.3.

Workup

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

Sources & evidence

ORD record
ord-51ce7569c835425d8df91f44f7e2b501
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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