Hydrochloric Acid → HCID 67367161, compound

HRID 1877435Notes

Reaction equation

HRID 1877435 reaction equation
C[O:2][C:3](=[O:34])[C:4]1[CH:9]=[C:8]([Cl:10])[C:7]([O:11][C:12]2[C:17]([C:18]([N:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]([CH:30]4[CH2:32][CH2:31]4)[CH2:22][CH2:21]3)=[O:19])=[CH:16][CH:15]=[CH:14][N:13]=2)=[CH:6][C:5]=1[Cl:33].C1COCC1.[OH-].[Li+].Cl>O.CO>[Cl:33][C:5]1[CH:6]=[C:7]([O:11][C:12]2[C:17]([C:18]([N:20]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[N:23]([CH:30]4[CH2:31][CH2:32]4)[CH2:22][CH2:21]3)=[O:19])=[CH:16][CH:15]=[CH:14][N:13]=2)[C:8]([Cl:10])=[CH:9][C:4]=1[C:3]([OH:34])=[O:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 59294520HCID 59294520, compound

Product 1

HCID 67367161HCID 67367161, compoundYield 82.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

To a solution of 2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-benzoic acid methyl ester (50 mg, 0.10 mmol, 1.0 equiv; Example 182) in a 2:2:1 mixture of THF, methanol and water (2 mL) was added lithium hydroxide (4.8 mg, 0.20 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 heptane/ethyl acetate to give 40 mg (82%) of the title compound as a light yellow solid. MS (ISN): 482.0 [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 heptane/ethyl acetate

Sources & evidence

ORD record
ord-0408d2569ce144e4adeaa72207543736
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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