Sulfuric Acid → Methyl 4-amino-6-(4-chlorophenyl)-5-fluoropicolinate

HRID 1774286Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:11]=[C:10]([N:18]=C3C=CC(=O)C=C3)[C:9]=2[F:26])=[CH:4][CH:3]=1.OS(O)(=O)=O.CC#N.O.C(Cl)Cl>CCOC(C)=O.CCCCCC>[NH2:18][C:10]1[C:9]([F:26])=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[N:13]=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:11]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of methyl 6-(4-chlorophenyl)-5-fluoro-4-((4-oxocyclohexa-2,5-dien-1-ylidene)amino)picolinate (0.074 g, 0.20 mmol) and 0.1 M H2SO4 (0.2 mL) in a 1:1 mixture of CH3CN/H2O (2 mL) was heated to 80° C. for 1 h. After stirring at room temperature for 2 h, the reaction mixture was added to CH2Cl2 (10 mL). The organic layer was washed with a saturated solution of NaCl and dried (MgSO4), and the solvent was removed. Preparative TLC on silica gel eluting with 20% EtOAc/hexane gave methyl 4-amino-6-(4-chlorophenyl)-5-fluoropicolinate (0.050 g, 0.169 mmol, 85% yield) as a light yellow solid: 1H NMR (400 MHz, CDCl3) δ 7.83 (m, 2H), 7.45 (d, J=6.2 Hz, 1H), 7.37 (m, 2H), 4.40 (br s, 2H), 3.90 (s, 3H). ESIMS m/z 279.77 ([M−H]−); 19F NMR (376 MHz, CDCl3) δ −145.11.

Workup

washThe organic layer was washed with a saturated solution of NaCl
dry with materialdried (MgSO4)
customthe solvent was removed

Sources & evidence

ORD record: ord-8f13562a1f3d4aba94fc1375c772cab5
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09260392B2

Reaction notes

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