Potassium Phosphate, Tribasic → (S)-methyl 2-(2,4-difluorophenyl)-3-(2-methylpiperidin-1-yl)quinoxaline-6-carboxylate

HRID 1403573Notes

Reaction equation

[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1B(O)O.[CH3:12][C@H:13]1[CH2:18][CH2:17][CH2:16][CH2:15][N:14]1[C:19]1[C:20](OS(C(F)(F)F)(=O)=O)=[N:21][C:22]2[C:27]([N:28]=1)=[CH:26][C:25]([C:29]([O:31][CH3:32])=[O:30])=[CH:24][CH:23]=2.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:20]1[C:19]([N:14]2[CH2:15][CH2:16][CH2:17][CH2:18][C@@H:13]2[CH3:12])=[N:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25]([C:29]([O:31][CH3:32])=[O:30])[CH:26]=2)[N:21]=1

Participants

Conditions

Temperature: 95 °C

Procedure

To a solution of (2,4-difluorophenyl)boronic acid (218.9 mg, 1.39 mmol) in dioxane (5.0 mL) and water (3 drops) was added (S)-methyl 3-(2-methylpiperidin-1-yl)-2-(trifluoromethylsulfonyloxy)quinoxaline-6-carboxylate (300 mg, 0.69 mmol), K3PO4 (293 mg, 1.38 mmol) and Pd(PPh3)4 (39.97 mg, 0.03 mmol) with stirring for 1 hour at 95° C. in an oil bath under an inert atmosphere of nitrogen. The reaction mixture was concentrated in vacuo to give a residue, which was purified via silica gel column chromatography (2% ethyl acetate in petroleum ether) to afford (S)-methyl 2-(2,4-difluorophenyl)-3-(2-methylpiperidin-1-yl)quinoxaline-6-carboxylate as a light yellow solid (192.0 mg, 70%)

Workup

concentrationThe reaction mixture was concentrated in vacuo
customto give a residue, which
customwas purified via silica gel column chromatography (2% ethyl acetate in petroleum ether)

Sources & evidence

ORD record: ord-2f92626ca7a249d4aa157fee4b0ec37a
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912188B2

Reaction notes

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