Lithium Hydroxide → HCID 118307857, compound

HRID 718432Notes

Reaction equation

HRID 718432 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:43])=[N:14][C:15]([CH3:42])=[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])=[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].[Li+].[OH-]>CCO.O>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:43])=[N:14][C:15]([CH3:42])=[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])=[CH:37][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])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118314211HCID 118314211, compound

Product 1

HCID 118307857HCID 118307857, compoundYield 94%

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-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.009 g, 0.015 mmol) and LiOH (3.65 mg, 0.152 mmol) in 9:1 EtOH/H2O (1 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-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetic acid (0.0081 g, 0.014 mmol, 94% yield) as white solid. Alternatively, to a solution of (S)-isopropyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(4-fluorophenethoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.302 g, 0.5 mmol) in ethanol (5 mL) and water (0.500 mL) was added KOH (0.281 g, 5.00 mmol). The solution was heated at 75° C. for 8 h. The solvent in the mixture was evaporated. The remaining residue was treated with water (5 mL), and acidified with 1 N HCl (5.1 mL) to pH˜2. The resulting mixture was stirred for 1 h. The solid was collected on a filter, washed with water, dried under vacuum to give (0.281 g, 100%) as beige solid. 1H NMR (500 MHz, CDCl3) δ 7.27-7.32 (m, 2H), 7.12-7.18 (m, 1H), 7.01-7.09 (m, 3H), 6.95-7.00 (m, 2H), 5.95 (br. s., 1H), 4.16-4.29 (m, 2H), 3.61 (br. s., 1H), 3.13 (t, J=6.9 Hz, 2H), 2.77-3.02 (m, 1H), 2.66 (s, 3H), 2.22 (s, 3H), 1.99-2.37 (m, 2H), 1.25 (s, 9H), 1.07-1.40 (m, 4H), 0.88 (br.s., 3H), 0.68 (br. s., 3H). LCMS (M+H)=563.3.

Workup

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

Sources & evidence

ORD record
ord-dc39fb167892455eb6ac5555ab07e5fb
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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