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

HRID 1877430Notes

Reaction equation

HRID 1877430 reaction equation
C([O:3][C:4](=[O:37])[CH:5]=[CH:6][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][CH:18]=[CH:17][N:16]=2)=[CH:9][C:8]=1[Cl:36])C.C1COCC1.[OH-].[Na+].Cl>O>[Cl:36][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[CH2:34][CH2:35]4)[CH2:25][CH2:24]3)=[O:22])=[CH:19][CH:18]=[CH:17][N:16]=2)[C:11]([Cl:13])=[CH:12][C:7]=1[CH:6]=[CH:5][C:4]([OH:37])=[O:3]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 673681563-{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-acrylic acid ethyl ester

Product 1

HCID 673687943-{2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-acrylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of 3-{2,5-dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-2-yloxy]-phenyl}-acrylic acid ethyl ester (74 mg, 0.14 mmol, 1.0 equiv) in a 1:1 mixture of THF and water (2 mL) was added sodium hydroxide (11 mg, 0.28 mmol, 2.0 equiv; [CAS RN 1310-73-2]) and the reaction mixture heated by microwave irradiation to 100° C. for 10 min. 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 preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column equipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps, a Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water yielding 21 mg (30%) of the title compound as a yellow viscous oil. MS (ISP): 509.9 [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 preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  5. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  6. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water yielding 21 mg (30%) of the title compound as a yellow viscous oil

Sources & evidence

ORD record
ord-d0dcd3738ea143f597ed21fee5cb9647
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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