Potassium Carbonate → 4-Trifluoromethoxybenzyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoropicolinate

HRID 333645

Reaction equation

[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([O:16][CH3:17])[C:10]=2[F:18])[N:5]=[C:4]([C:19]([OH:21])=[O:20])[C:3]=1[Cl:22].Br[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][C:32]([F:35])([F:34])[F:33])=[CH:27][CH:26]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[C:11]([O:16][CH3:17])[C:10]=2[F:18])[N:5]=[C:4]([C:19]([O:21][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][C:32]([F:33])([F:34])[F:35])=[CH:27][CH:26]=2)=[O:20])[C:3]=1[Cl:22]

Participants

Conditions

Temperature: 50 °C

Procedure

A suspension of 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-5-fluoropicolinic acid (200 mg, 0.573 mmol), 1-(bromomethyl)-4-(trifluoromethoxy)benzene (161 mg, 0.630 mmol) and K2CO3 (119 mg, 0.859 mmol) in DMF (2 mL) was heated at 50° C. overnight. The reaction mixture was then concentrated in vacuo. The residue was purified by silica gel chromatography (eluting with 0-80% EtOAc/hexane gradient) to yield a white solid (154 mg, 51.4%): mp 155-156° C.; 1H NMR (400 MHz, DMSO-d6) δ 7.60 (d, J=8.7 Hz, 2H), 7.47 (dd, J=8.5, 1.5 Hz, 1H), 7.41 (d, J=8.0 Hz, 2H), 7.29 (dd, J=8.5, 7.1 Hz, 1H), 7.14 (s, 2H), 5.41 (s, 2H), 3.95-3.90 (m, 3H); ESIMS m/z 523 ([M+H]+), 521 ([M−H]−).

Workup

concentrationThe reaction mixture was then concentrated in vacuo
customThe residue was purified by silica gel chromatography (eluting with 0-80% EtOAc/hexane gradient)

Sources & evidence

ORD record: ord-919561cd133b4be89dccc18d48b3f043
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08883688B2

Linked notes

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