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

HRID 718423Notes

Reaction equation

HRID 718423 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][C:37]([F:40])=[CH:36][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][C:37]([F:40])=[CH:36][CH:35]=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])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118314204(S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate

Product 1

HCID 118307750(2S)-2-tert-butoxy-2-[4-(4,4-dimethyl-1-piperidyl)-5-[4-[(4-fluorophenyl)methoxy]phenyl]-2,6-dimethyl-3-pyridyl]acetic acidYield 90%

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-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.0372 g, 0.065 mmol) and LiOH (0.015 g, 0.645 mmol) in 9:1 EtOH/H2O (2 mL) was refluxed for 2 h. Then, cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-((4-fluorobenzyl)oxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid (0.0318 g, 0.058 mmol, 90% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 7.43-7.49 (m, 2H), 7.15-7.19 (m, 1H), 7.09-7.14 (m, 2H), 7.02-7.08 (m, 3H), 5.78 (br. s., 1H), 5.07-5.15 (m, 2H), 2.74 (s, 3H), 2.28 (s, 3H), 1.25-1.37 (m, 4H), 1.23 (s, 9H), 0.78 (br. s., 6H). 4H of piperidine are missing. LCMS (M+H)=549.5.

Workup

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

Sources & evidence

ORD record
ord-3a5a7274af32469daaf56d0f8e6792b6
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

Loading…