Sodium Hydroxide → HCID 67287184, compound

HRID 1626521Notes

Reaction equation

HRID 1626521 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:37])[NH:20][C:21]3[N:22]=[N:23][C:24]([C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=4)=[CH:25][CH:26]=3)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:38]([O:40]CC)=[O:39].[OH-].[Na+]>C1COCC1.CCO>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:37])[NH:20][C:21]3[N:22]=[N:23][C:24]([C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=4)=[CH:25][CH:26]=3)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:38]([OH:40])=[O:39]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67288216HCID 67288216, compound

Product 1

HCID 67287184HCID 67287184, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

To a solution of ethyl 6-chloro-7-(4-(6-(4-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylate (1.83 g, 3.07 mmol) in 40 mL of 3:1 THF/EtOH was added sodium hydroxide (12.3 ml, 12.3 mmol). The reaction was stirred for 3 hours, then concentrated. The crude material was combined with 1M HCl (50 mL) and stirred for 3 hours. The material was resolved via supercritical fluid chromatography employing a CHIRALCEL® OJ-H column (3×15 cm) eluting with 35% ethanol/carbon dioxide at 100 bar, using 3 mL injections and a flow rate of 140 mL/min. Collection of fractions containing peak 2 and removal of volatiles provided Enantiomer 2 of 6-chloro-7-(4-(6-(4-(trifluoromethyl)phenyl)pyridazin-3-ylcarbamoyl)phenoxy)chroman-4-carboxylic acid (0.730 g, 1.29 mmol, 41.9% yield) as a white solid. MS (apci, positive) m/z=569.9.

Workup

  1. concentrationconcentrated
  2. stirringstirred for 3 hours
  3. washeluting with 35% ethanol/carbon dioxide at 100 bar
  4. customCollection of fractions
  5. additioncontaining
  6. custompeak 2 and removal of volatiles

Sources & evidence

ORD record
ord-6758df9adae14bcfa50b571d6f64e54e
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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