Lithium Hydroxide → [8-Chloro-4-difluoromethoxy-2-ethyl-3-(4-isobutylbenzyl)quinolin-5-yloxy]acetic acid

HRID 1944319Notes

Reaction equation

HRID 1944319 reaction equation
C[O:2][C:3](=[O:35])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]([Cl:16])=[C:12]2[C:7]=1[C:8]([O:31][CH:32]([F:34])[F:33])=[C:9]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([C:26](=O)[CH:27]([CH3:29])[CH3:28])=[CH:22][CH:21]=1)[C:10]([CH2:17][CH3:18])=[N:11]2.[OH-].[Li+]>O1CCCC1.O>[Cl:16][C:13]1[CH:14]=[CH:15][C:6]([O:5][CH2:4][C:3]([OH:35])=[O:2])=[C:7]2[C:12]=1[N:11]=[C:10]([CH2:17][CH3:18])[C:9]([CH2:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:26][CH:27]([CH3:28])[CH3:29])=[CH:24][CH:25]=1)=[C:8]2[O:31][CH:32]([F:34])[F:33]

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 67458281[8-Chloro-4-difluoromethoxy-2-ethyl-3-(4-isobutyrylbenzyl)quinolin-5-yloxy]acetic acid methyl ester

Product 1

HCID 68107147[8-Chloro-4-difluoromethoxy-2-ethyl-3-(4-isobutylbenzyl)quinolin-5-yloxy]acetic acidYield 86.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of [8-chloro-4-difluoromethoxy-2-ethyl-3-(4-isobutyrylbenzyl)quinolin-5-yloxy]acetic acid methyl ester (0.22 g) in tetrahydrofuran (5.0 mL) and water (1.0 mL) was treated with 1.0M aqueous lithium hydroxide solution (0.86 mL), and the resulting mixture was stirred at room temperature for 2 hours. The mixture was concentrated to low bulk under reduced pressure, and the pH adjusted to 4-5 by the addition of 1.0M aqueous hydrochloric acid solution. The mixture was extracted with ethyl acetate, and the combined extracts were dried over magnesium sulfate and then concentrated under reduced pressure. Purification of the residue by preparative reverse-phase HPLC gave title compound (0.18 g).

Workup

  1. concentrationThe mixture was concentrated to low bulk under reduced pressure
  2. additionthe pH adjusted to 4-5 by the addition of 1.0M aqueous hydrochloric acid solution
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialthe combined extracts were dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue by preparative reverse-phase HPLC

Sources & evidence

ORD record
ord-1a150a4a4c4e4749baed65d6b7d05481
Source dataset
uspto-grants-2013_03
Patent number
US08394830B2

Reaction notes

Loading…