Hydrochloric Acid → 2-Chloro-4-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenylethynyl}-benzoic acid

HRID 1877426Notes

Reaction equation

HRID 1877426 reaction equation
C[O:2][C:3](=[O:43])[C:4]1[CH:9]=[CH:8][C:7]([C:10]#[C:11][C:12]2[CH:17]=[C:16]([Cl:18])[C:15]([O:19][C:20]3[C:25]([C:26]([N:28]4[C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[N:31]([CH:38]5[CH2:40][CH2:39]5)[CH2:30][CH2:29]4)=[O:27])=[CH:24][CH:23]=[CH:22][N:21]=3)=[CH:14][C:13]=2[Cl:41])=[CH:6][C:5]=1[Cl:42].C1COCC1.[OH-].[Li+].Cl>O.CO>[Cl:42][C:5]1[CH:6]=[C:7]([C:10]#[C:11][C:12]2[CH:17]=[C:16]([Cl:18])[C:15]([O:19][C:20]3[C:25]([C:26]([N:28]4[C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[N:31]([CH:38]5[CH2:40][CH2:39]5)[CH2:30][CH2:29]4)=[O:27])=[CH:24][CH:23]=[CH:22][N:21]=3)=[CH:14][C:13]=2[Cl:41])[CH:8]=[CH:9][C:4]=1[C:3]([OH:43])=[O:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 592945182-Chloro-4-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenylethynyl}-benzoic acid methyl ester

Product 1

HCID 592945422-Chloro-4-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenylethynyl}-benzoic acidYield 75%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To a solution of 2-chloro-4-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenylethynyl}-benzoic acid methyl ester (150 mg, 0.24 mmol, 1.0 equiv; Example 167) in a 2:2:1 mixture of THF, methanol and water (2 mL) was added lithium hydroxide (11.4 mg, 0.47 mmol, 2.0 equiv; [CAS RN 1310-65-2]) and the reaction mixture stirred at rt over night. The crude reaction product was taken up in water (50 mL), acidified to pH 1 by addition of a solution of 1 M HCl and extracted with ethyl acetate (3×40 mL). The combined organic phases were dried over MgSO4 and the product purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of dichloromethane/methanol to give 110 mg (75%) of the title compound as a light brown solid. MS (ISN): 616.1 [M−H]−.

Workup

  1. customThe crude reaction product
  2. extractionextracted with ethyl acetate (3×40 mL)
  3. dry with materialThe combined organic phases were dried over MgSO4
  4. customthe product purified by silica column chromatography
  5. washeluting with a gradient of dichloromethane/methanol

Sources & evidence

ORD record
ord-ed88b1f4b16a4c95a176d7758f869a6d
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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