Toluene → HCID 86709869, compound

HRID 541047Notes

Reaction equation

HRID 541047 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:14](O)=[O:15])[CH:11]=[C:10]([Cl:17])[C:9]=2[Cl:18])=[C:4]([F:19])[C:3]=1[O:20][CH3:21].S(Cl)([Cl:24])=O.C1(C)C=CC=CC=1>CN(C)C1C=CN=CC=1.CN(C)C=O.C(#N)C.CO>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:14]([Cl:24])=[O:15])[CH:11]=[C:10]([Cl:17])[C:9]=2[Cl:18])=[C:4]([F:19])[C:3]=1[O:20][CH3:21]

Participants

8

Reactant 3

HCID 1140TolueneHCID 24386Thionyl Chloride2×HCID 867098682-Pyridinecarboxylic acid, 4,5-dichloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-

Product 1

HCID 86709869HCID 86709869, compoundYield 95%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent2×HCID 6342AcetonitrileSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 33.5 g (˜95 mmol) of 6-(4-chloro-2-fluoro-3-methoxyphenyl)-4,5-dichloro-2-pyridinecarboxylic acid, 10.2 mL (140 mmol) of thionyl chloride, 0.1 mL of N,N-dimethylforamide (DMF) and 200 mL of toluene was heated at 75° C. for 5 h. The reaction progress was monitored by conversion of the acid chloride to its methyl ester (one drop of reaction mixture added to 5 drops of a 10% wt methanol solution containing 4-(dimethylamino)pyridine, briefly heating to reflux, dilution with acetonitrile and injection). LC analysis indicated 8 area % remaining carboxylic acid and 3 area % of an unidentified closely following product. Another 5 mL of thionyl chloride and 0.1 mL of DMF were added, and heating continued for an additional 2 h. LC analysis indicated methyl ester product, carboxylic acid gone with only the unidentified polar peak remaining After stirring at RT overnight, the reaction mixture was filtered to remove a small amount of an insoluble material. The filtrate was concentrated in vacuo, and toluene added twice and re-concentrated in vacuo to evaporate residual thionyl chloride. The white solid (38.6 g) was dried in a vacuum oven at 40° C. to give 33.3 g of title compound (mp 134-136° C.). LC internal standard analysis (conversion to its methyl ester as described above) indicated 98.1 wt %. EIMS m/e (relative intensity) 369 (4Cl, 80), 332 (3Cl, 38), 304 (3Cl, 82), 269 (2Cl, 100), 254 (2Cl, 30), 226 (2Cl, 73), 191 (30), 156 (46); 1H NMR (400 MHz, CDCl3) δ 8.23 (s, 1H), 7.32 (dd, J=8, 2 Hz, 1H), 7.15 (dd, J=8, 7 Hz, 1H), 4.02 (dd, J=1 Hz, 3H); 19F NMR (376 MHz, 1H decoupled, CDCl3) δ −126.83.

Workup

  1. customone drop of reaction mixture
  2. temperaturebriefly heating
  3. temperatureto reflux
  4. temperatureheating
  5. filtrationthe reaction mixture was filtered
  6. customto remove a small amount of an insoluble material
  7. concentrationThe filtrate was concentrated in vacuo, and toluene
  8. additionadded twice
  9. concentrationre-concentrated in vacuo
  10. customto evaporate residual thionyl chloride
  11. dry with materialThe white solid (38.6 g) was dried in a vacuum oven at 40° C.

Sources & evidence

ORD record
ord-6e8b95ad57a446eeada132fa37c39b27
Source dataset
uspto-grants-2014_10
Patent number
US08871943B2

Reaction notes

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