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

HRID 718424Notes

Reaction equation

HRID 718424 reaction equation
[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[C:16]([CH3:41])=[N:17][C:18]([CH3:40])=[C:19]([C@H:29]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:30]([O:32]CC)=[O:31])[C:20]=2[N:21]2[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-]>CCO.O>[CH2:1]([O:8][C:9]1[N:14]=[CH:13][C:12]([C:15]2[C:16]([CH3:41])=[N:17][C:18]([CH3:40])=[C:19]([C@H:29]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[C:30]([OH:32])=[O:31])[C:20]=2[N:21]2[CH2:26][CH2:25][C:24]([CH3:28])([CH3:27])[CH2:23][CH2:22]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 118336859(S)-ethyl 2-(6'-(benzyloxy)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-[3,3'-bipyridin]-5-yl)-2-(tert-butoxy)acetate

Product 1

HCID 118307735(2S)-2-[5-(6-benzyloxy-3-pyridyl)-4-(4,4-dimethyl-1-piperidyl)-2,6-dimethyl-3-pyridyl]-2-tert-butoxy-acetic acidYield 68%

Reagents, catalysts & solvents 1

HCID 19096565Water ethanolSolvent

Procedure

A solution of (S)-ethyl 2-(6′-(benzyloxy)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-[3,3′-bipyridin]-5-yl)-2-(tert-butoxy)acetate (0.014 g, 0.025 mmol) and LiOH (5.99 mg, 0.250 mmol) in 9:1 EtOH/H2O (2 mL) was refluxed for 3 h. Then, cooled and purified by prep-HPLC to afford (S)-2-(6′-(benzyloxy)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-[3,3′-bipyridin]-5-yl)-2-(tert-butoxy)acetic acid (0.0089 g, 0.017 mmol, 66.9% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ 8.08 (d, J=2.2 Hz, 0.5H), 7.99 (d, J=1.7 Hz, 0.5H), 7.46-7.54 (m, 3H), 7.33-7.45 (m, 3H), 6.94 (dd, J=5.8, 8.4 Hz, 1H), 5.93 (br. s., 1H), 5.40-5.55 (m, 2H), 3.40-3.70 (m, 0.5H), 2.74-3.11 (m, 0.5H), 2.67 (s, 3H), 2.28 (s, 1.5H), 2.25 (s, 1.5H), 1.94-2.20 (m, 1H), 1.27-1.40 (m, 4H), 1.25 (s, 4.5H), 1.24 (s, 4.5H), 0.80 (br.s., 6H). LCMS (M+H)=532.4.

Workup

  1. temperatureThen, cooled
  2. custompurified by prep-HPLC

Sources & evidence

ORD record
ord-90f2786aa5404e0698ad582543aa0d5c
Source dataset
uspto-grants-2015_11
Patent number
US09193720B2

Reaction notes

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