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

HRID 718428Notes

Reaction equation

HRID 718428 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:42])=[N:14][C:15]([CH3:41])=[C:16]([C:26]2[CH:31]=[CH:30][C:29]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=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]([CH3:42])=[N:14][C:15]([CH3:41])=[C:16]([C:26]2[CH:27]=[CH:28][C:29]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([F:40])[CH:35]=3)=[CH:30][CH:31]=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])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118314209(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((3-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307801(2S)-2-tert-butoxy-2-[4-(4,4-dimethyl-1-piperidyl)-5-[4-[(3-fluorophenyl)methoxy]phenyl]-2,6-dimethyl-3-pyridyl]acetic acidYield 87.5%

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-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.0325 g, 0.056 mmol) and LiOH (0.013 g, 0.564 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-((3-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid (0.0269 g, 0.049 mmol, 87% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.39 (dt, J=5.8, 7.9 Hz, 1H), 7.25 (d, J=7.7 Hz, 1H), 7.16-7.23 (m, 2H), 7.01-7.10 (m, 4H), 5.95 (br. s., 1H), 5.12-5.19 (m, 2H), 3.62 (br. s., 1H), 2.88 (br. s., 1H), 2.65 (s, 3H), 2.23 (s, 3H), 1.24 (s, 9H), 0.87 (br.s., 3H), 0.67 (br. s., 3H). 6H of piperidine were not resolved. LCMS (M+H)=549.4.

Workup

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

Sources & evidence

ORD record
ord-5c6e2ca091ab460ea9211a26d32fcc08
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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