Water → 2,4-Dichlorobenzyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinate

HRID 1754135Notes

Reaction equation

HRID 1754135 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([O:15][CH3:16])[C:9]=2[F:17])[N:5]=[C:4]([C:18]([OH:20])=[O:19])[C:3]=1[Cl:21].[H-].[Na+].[Cl:24][C:25]1[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:26]=1[CH2:32]Cl.O>CN(C=O)C>[NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([O:15][CH3:16])[C:9]=2[F:17])[N:5]=[C:4]([C:18]([O:20][CH2:32][C:26]2[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:25]=2[Cl:24])=[O:19])[C:3]=1[Cl:21]

Participants

6

Reactant 4

HCID 962WaterHCID 72122,4-Dichlorobenzyl chlorideHCID 24758Sodium hydrideHCID 25181547Halauxifen

Product 1

HCID 704986622,4-Dichlorobenzyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinateYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

4-Amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinic acid (prepared by the methods described in U.S. Pat. No. 7,314,849 B2; 828 mg, 2.5 mmol) was dissolved in DMF (4 mL). Sodium hydride (NaH, 60% dispersion in mineral oil; 154 mg, 3.85 mmol) was added portion wise. To the mixture was added 2,4-dichloro-1-(chloromethyl)benzene (586 mg, 3.0 mmol). The reaction mixture was allowed to stir for 24 hours (h). Water was added to the reaction mixture, and the aqueous phase was extracted with EtOAc (×3). The combined organic extracts were washed with brine, dried with Na2SO4, filtered, and concentrated. Purification by normal phase chromatography gave a white solid (440 mg, 35%): mp 165-168° C., 1H NMR (400 MHz, CDCl3) δ 7.68 (dd, J=8.6, 7.8 Hz, 1H), 7.54 (d, J=8.3 Hz, 1H), 7.43 (d, J=2.1 Hz, 1H), 7.28 (d, J=2.1 Hz, 1H), 7.23 (d, J=1.8 Hz, 1H), 7.21 (d, J=1.6 Hz, 1H), 5.50 (s, 2H), 4.83 (s, 2H), 3.97 (d, J=0.8 Hz, 3H); ESIMS m/z 489 ([M−H]).

Workup

  1. extractionthe aqueous phase was extracted with EtOAc (×3)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by normal phase chromatography

Sources & evidence

ORD record
ord-3b755fd5706e4ceea80c2e32950b3130
Source dataset
uspto-grants-2015_10
Patent number
US09169217B2

Reaction notes

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