Potassium Fluoride → Methyl 4-amino-6-(4-chlorophenyl)-5-fluoro-3-methoxypicolinate

HRID 407237

Reaction equation

HRID 407237 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6](Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15].[Cl:16][C:17]1[CH:22]=[CH:21][C:20](B2OCCCO2)=[CH:19][CH:18]=1.[F-].[K+].C1C=C(S([O-])(=O)=O)C=C(P(C2C=CC=C(S([O-])(=O)=O)C=2)C2C=CC=C(S([O-])(=O)=O)C=2)C=1.[Na+].[Na+].[Na+]>CC#N.O.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:20]2[CH:21]=[CH:22][C:17]([Cl:16])=[CH:18][CH:19]=2)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[C:3]=1[O:14][CH3:15]

Participants

9

Reactant 4

HCID 522689Potassium FluorideHCID 34689572-(4-Chlorophenyl)-1,3,2-dioxaborinaneHCID 6099338Trisodium 3,3',3''-phosphinetriyltris(benzene-1-sulphonate)HCID 86675409Methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate

Product 1

HCID 71150696Methyl 4-amino-6-(4-chlorophenyl)-5-fluoro-3-methoxypicolinateYield 72.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of methyl 4-amino-6-chloro-5-fluoro-3-methoxypicolinate (200 mg, 0.852 mmol) in CH3CN (1.246 mL) and H2O (1.246 mL) were added 2-(4-chlorophenyl)-1,3,2-dioxaborinane (251 mg, 1.279 mmol), KF (149 mg, 2.56 mmol), palladium(II) acetate (Pd(OAc)2; 19.14 mg, 0.085 mmol), and triphenylphosphine-3,3′,3″-trisulfonic acid trisodium salt (100 mg, 0.170 mmol). The reaction mixture was then heated in a bench top Biotage microwave at 150° C. for 5 min. The reaction mixture was diluted with CH2Cl2 and washed with H2O. The organic layer was separated, dried over MgSO4, filtered and concentrated. The crude residue was purified by normal phase chromatography (eluting with 10% EtOAc/40% CH2Cl2/50% hexanes) to afford the title compound as a tan solid (191 mg, 72.1%): mp 93-94° C.; 1H NMR (400 MHz, acetone-d6) δ 7.96 (dd, J=8.8, 1.4 Hz, 2H), 7.57-7.49 (m, 2H), 5.93 (s, 2H), 3.92 (s, 3H), 3.91 (s, 3H), ESIMS m/z 311 ([M+H]+), 309 ([M−H]−).

Workup

  1. washwashed with H2O
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by normal phase chromatography (eluting with 10% EtOAc/40% CH2Cl2/50% hexanes)

Sources & evidence

ORD record
ord-9c18d074a7144da5a2d778269b02827d
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Linked notes

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