Sodium Hydroxide → {4-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-acetic acid

HRID 1877413Notes

Reaction equation

HRID 1877413 reaction equation
C([O:3][C:4](=[O:34])[CH2:5][N:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]([C:16]([C:18]2[C:19]([O:25][C:26]3[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:27]=3[Cl:33])=[N:20][CH:21]=[C:22]([F:24])[CH:23]=2)=[O:17])[CH2:8][CH2:7]1)C.[OH-].[Na+]>C1COCC1>[Cl:33][C:27]1[CH:28]=[CH:29][C:30]([Cl:32])=[CH:31][C:26]=1[O:25][C:19]1[C:18]([C:16]([N:9]2[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[N:6]([CH2:5][C:4]([OH:34])=[O:3])[CH2:7][CH2:8]2)=[O:17])=[CH:23][C:22]([F:24])=[CH:21][N:20]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 59294509{4-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-acetic acid ethyl ester

Product 1

HCID 59294465{4-[2-(2,5-Dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-acetic acidYield 10%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of {4-[2-(2,5-dichloro-phenoxy)-5-fluoro-pyridine-3-carbonyl]-3,4-dihydro-2H-quinoxalin-1-yl}-acetic acid ethyl ester (82 mg, 0.163 mmol, 1.0 equiv; Example 154) in THF (1 mL) was added a 5 M solution of sodium hydroxide (0.5 mL, 2.5 mmol, 15 equiv; [CAS RN 1310-73-2]) and the reaction mixture heated by microwave irradiation to 120° C. for 30 min. Removal of the solvent under reduced pressure and purification 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 provided 7.5 mg (10%) of the title compound as a light yellow powder. MS (ISP): 476.0 [M+H]+.

Workup

  1. customRemoval of the solvent
  2. customunder reduced pressure and purification by preparative HPLC on reversed phase (Xterra® PrepMSC 18, 5 μm, 19×50 mm column
  3. customequipped with a Gilson Liquid Handler 215 autosampler, two Rainin Dynamax® SD-300 pumps
  4. washa Sedex ELSD 75 lightscatter and a Dionex UVD 340S UV detector) eluting with a gradient of acetonitrile/water

Sources & evidence

ORD record
ord-f3e2f60916e648b2b493eee9fdaaeae5
Source dataset
uspto-grants-2012_11
Patent number
US08309734B2

Reaction notes

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