Dichloroacetic Acid → {1-[3-(aminocarbonyl)phenyl]-5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxo-1,6-dihydropyridin-2-yl}methyl Acetate

HRID 1867167Notes

Reaction equation

HRID 1867167 reaction equation
[C:1]([O:4][CH2:5][C:6]1[N:7]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH2:31])=[O:30])[CH:24]=2)[C:8](=[O:22])[CH:9]=[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[CH:11]=1)(=[O:3])[CH3:2].[Cl:32]N1C(=O)CCC1=O.ClC(Cl)C(O)=O>ClCCl.C(OCC)C>[C:1]([O:4][CH2:5][C:6]1[N:7]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH2:31])=[O:30])[CH:24]=2)[C:8](=[O:22])[C:9]([Cl:32])=[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][C:15]=2[F:21])[CH:11]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 3

HCID 6597Dichloroacetic AcidHCID 31398ChlorosuccinimideHCID 22050389{1-[3-(Aminocarbonyl)phenyl]-4-[(2,4-difluorobenzyl)oxy]-6-oxo-1,6-dihydropyridin-2-yl}methyl acetate

Product 1

HCID 22050051{1-[3-(aminocarbonyl)phenyl]-5-chloro-4-[(2,4-difluorobenzyl)oxy]-6-oxo-1,6-dihydropyridin-2-yl}methyl AcetateYield 85%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

{1-[3-(aminocarbonyl)phenyl]-4-[(2,4-difluorobenzyl)oxy]-6-oxo-1,6-dihydropyridin-2-yl}methyl acetate (from step 2) (1.02 g, 2.39 mmol) was suspended in dichloromethane (15 mL) and N-chlorosuccinimide (0.37 g, 2.75 mmol) was added. Dichloroacetic acid (0.10 ml, 1.22 mmol) was added and the reaction mixture was stirred at 40° C. for 1.5 hours. The reaction was cooled to room temperature and a precipitate formed. The reaction mixture was diluted with diethyl ether and the precipitate was collected by filtration and washed with diethyl ether (3×15 mL) to afford a tan solid (0.940 g, 85%). 1H NMR (400 MHz, DMF-d6) δ 8.21 (br s, 1H), 8.11 (app dt, J=1.48, 7.52 Hz, 1H), 7.95 (app t, J=1.61 Hz, 1H), 7.80 (app dt, J=6.72, 8.59 Hz, 1H) 7.69-7.60 (m, 2H), 7.48 (br s, 1H), 7.35 (ddd, J=2.55, 9.53, 10.61 Hz, 1H), 7.24-7.19 (m, 1H), 6.97 (s, 1H), 5.49 (s, 2H), 4.71 (AB q, JAB=15.04 Hz, 2H), 198 (s, 3H). ES-HRMS m/z 463.0883 (M+H calcd for C22H17ClF2N2O5 requires 463.0867).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customa precipitate formed
  3. filtrationthe precipitate was collected by filtration
  4. washwashed with diethyl ether (3×15 mL)

Sources & evidence

ORD record
ord-5220077c08b94353897610910510c032
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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