Hydrochloric Acid → {2,5-Dichloro-4-[5-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-2-methyl-pyridin-4-yloxy]-benzoylamino}-acetic acid

HRID 1025896Notes

Reaction equation

HRID 1025896 reaction equation
C[O:2][C:3](=[O:39])[CH2:4][NH:5][C:6](=[O:38])[C:7]1[CH:12]=[C:11]([Cl:13])[C:10]([O:14][C:15]2[C:20]([C:21]([N:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:26]([CH:33]4[CH2:35][CH2:34]4)[CH2:25][CH2:24]3)=[O:22])=[CH:19][N:18]=[C:17]([CH3:36])[CH:16]=2)=[CH:9][C:8]=1[Cl:37].O.O.[OH-].[Li+].Cl>O1CCOCC1.C(OCC)(=O)C>[Cl:37][C:8]1[CH:9]=[C:10]([O:14][C:15]2[C:20]([C:21]([N:23]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[N:26]([CH:33]4[CH2:35][CH2:34]4)[CH2:25][CH2:24]3)=[O:22])=[CH:19][N:18]=[C:17]([CH3:36])[CH:16]=2)[C:11]([Cl:13])=[CH:12][C:7]=1[C:6]([NH:5][CH2:4][C:3]([OH:39])=[O:2])=[O:38]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 53311535{2,5-Dichloro-4-[5-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-2-methyl-pyridin-4-yloxy]-benzoylamino}-acetic acid methyl ester

Product 1

HCID 53311536{2,5-Dichloro-4-[5-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-2-methyl-pyridin-4-yloxy]-benzoylamino}-acetic acidYield 27%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 38 mg (0.067 mmol) {2,5-dichloro-4-[5-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-2-methyl-pyridin-4-yloxy]-benzoylamino}-acetic acid methyl ester (Example 69) in 2 mL dioxane was added 2 mL water and 4 mg (0.083 mmol) lithium hydroxide monohydrate. The reaction mixture was stirred at room temperature for 4 hours and then poured on 20 mL 1N aqueous hydrochloric acid and 20 mL ethyl acetate. The layers were separated and the aqueous layer was extracted a second time with 20 mL ethyl acetate. The combined organic layers were washed with 30 mL brine, dried over magnesium sulfate, filtered and concentrated under vacuum to yield 10 mg (27%) of the desired compound as a light yellow solid. MS (ESI): m/z=555.119 [M+H]+.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted a second time with 20 mL ethyl acetate
  3. washThe combined organic layers were washed with 30 mL brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-ffd8b34f11684174a6f8d160b332babc
Source dataset
uspto-grants-2014_05
Patent number
US08729091B2

Reaction notes

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