Hydrochloric Acid → HCID 86727251, compound

HRID 2173055Notes

Reaction equation

[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[C:8]([F:12])=[C:7](/[CH:13]=[N:14]/[CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=2[O:24][CH3:25])[C:3]=1[C:4]([OH:6])=O.[CH3:26][Li].Cl>C1COCC1>[Cl:1][C:2]1[C:3]2[C:4](=[O:6])[N:14]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][C:17]=3[O:24][CH3:25])[CH:13]([CH3:26])[C:7]=2[C:8]([F:12])=[C:9]([Cl:11])[N:10]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a mixture of (E)-2,6-dichloro-4-(((2,4-dimethoxybenzyl)imino)methyl)-5-fluoronicotinic acid (72.0 g, 186.5 mmol) in THF (700 mL) was added methyllithium (933.0 mL, 933.0 mmol) dropwise at −78° C. After the addition was complete, the solution was stirred for an additional 2 h. The reaction mixture was then acidified with 1N HCl to pH 6, heated to 50° C. for 7 h, and subsequently extracted with EtOAc. The organic layer was washed with brine and dried over anhydrous Na2SO4. The concentrated crude was purified by silica gel chromatography to give the title compound as a white solid (14 g, 15%). 1H NMR (CDCl3, 400 MHz) δ ppm 1.58 (d, J=6.8 Hz, 3H), 3.79 (s, 3H), 3.84 (s, 3H), 4.35 (d, J=14.4 Hz, 1H), 4.52 (q, J=6.8 Hz, 1H), 5.07 (d, J=14.4 Hz, 1H), 6.43-6.45 (m, 2H), 7.28 (d, J=9.2 Hz, 1H). [M+H] calc'd for C17H15Cl2FN2O3, 385. found, 385.

Workup

additionAfter the addition
extractionsubsequently extracted with EtOAc
washThe organic layer was washed with brine
dry with materialdried over anhydrous Na2SO4
concentrationThe concentrated crude
customwas purified by silica gel chromatography

Sources & evidence

ORD record: ord-0f83dce439b449099603377284b761a0
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09056873B2

Reaction notes

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