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

HRID 718433Notes

Reaction equation

HRID 718433 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]([F:41])=[C:37]([CH3:42])[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].[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][C:35]3[CH:40]=[CH:39][C:38]([F:41])=[C:37]([CH3:42])[CH:36]=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])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118314212(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-fluoro-3-methylphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307828(S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-fluoro-3-methylphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acidYield 89.7%

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-(4-fluoro-3-methylphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.035 g, 0.058 mmol) and LiOH (0.014 g, 0.579 mmol) in 9:1 EtOH/H2O (2 mL) 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-(4-fluoro-3-methylphenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid (0.0298 g, 0.052 mmol, 89% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.12-7.17 (m, 2H), 7.04-7.12 (m, 2H), 6.95-7.01 (m, 3H), 5.96 (br. s., 1H), 4.16-4.28 (m, 2H), 3.60 (br. s., 1H), 3.09 (t, J=7.0 Hz, 2H), 2.80-3.01 (m, 1H), 2.66 (s, 3H), 2.30 (d, J=1.7 Hz, 3H), 2.19-2.32 (m, 1H), 2.22 (s, 3H), 1.97-2.15 (m, 1H), 1.25 (s, 9H), 0.87 (br. s., 3H), 0.68 (br. s., 3H). 4H of piperidine were not resolved. LCMS (M+H)=577.3.

Workup

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

Sources & evidence

ORD record
ord-9c4ef333e8dd4a3d9c11f1ecfffbb9ac
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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