Methanol → Methyl 2,5-Dichloronicotinate

HRID 717813Notes

Reaction equation

HRID 717813 reaction equation
[Cl:1][C:2]1[N:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:12](Cl)(=O)C(Cl)=O.CO>ClCCl.CN(C)C=O>[Cl:1][C:2]1[N:10]=[CH:9][C:8]([Cl:11])=[CH:7][C:3]=1[C:4]([O:6][CH3:12])=[O:5]

Participants

6

Reactant 3

HCID 887MethanolHCID 65578Oxalyl chlorideHCID 27360852,5-Dichloropyridine-3-carboxylic acid

Product 1

HCID 2764318Methyl 2,5-DichloronicotinateYield 89%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

A solution of 2,5-dichloronicotinic acid (20 g, 0.10 mol) [OChem, 782D853] in dichloromethane (520 mL) was treated with 2 M oxalyl chloride in dichloromethane (160 mL, 310 mmol) followed by a few drops of N,N-dimethylformamide and stirred at 20° C. for 15 hours. The reaction mixture was concentrated, diluted with dichloromethane (200 mL), cooled to 0° C., treated with methanol (110 mL, 2.7 mol), and stirred at 0° C. for 5 minutes. The reaction mixture was concentrated to a crude residue. Purification by flash column chromatography using ethyl acetate in hexanes (0-80%) gave the desired product (19 g, 89%). LCMS calculated for C7H6Cl2NO2 (M+H)+: m/z=206.0, 208.0. found: 205.8, 207.7.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with dichloromethane (200 mL)
  3. temperaturecooled to 0° C.
  4. stirringstirred at 0° C. for 5 minutes
  5. concentrationThe reaction mixture was concentrated to a crude residue
  6. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-1a39b218c9b545c8a568b8b8c2ab387e
Source dataset
uspto-grants-2015_11
Patent number
US09193721B2

Reaction notes

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