Isopropanol → Isopropyl 4-Chloropicolinate

HRID 389616Notes

Reaction equation

HRID 389616 reaction equation
CN(C)C=O.C(Cl)(=O)C(Cl)=O.[Cl:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([C:19]([OH:21])=[O:20])[CH:14]=1.[CH:22](O)([CH3:24])[CH3:23]>ClCCl.C(=O)(O)[O-].[Na+].O>[CH:22]([O:20][C:19](=[O:21])[C:15]1[CH:14]=[C:13]([Cl:12])[CH:18]=[CH:17][N:16]=1)([CH3:24])[CH3:23]

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 6228Dimethylformamide2×HCID 65578Oxalyl chloride2×HCID 2308904-Chloropyridine-2-carboxylic acid

Product 1

HCID 59596919Isopropyl 4-ChloropicolinateYield 87%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent2×

Procedure

N,N-Dimethylformamide (0.3 mL) was added dropwise to a suspension of oxalyl chloride (6.6 mL, 76 mmol) and 4-chloropicolinic acid (10.0 g, 63.5 mmol) in dichloromethane (200 mL). The reaction mixture was stirred for 1 hour and additional oxalyl chloride (4 mL) and N,N-dimethylformamide (0.2 mL) was added. After a further 30 minutes, isopropanol (100 mL) was slowly added, followed by, after a further 15 minutes, solid sodium bicarbonate (12 g). The reaction mixture was diluted with 1:1 saturated sodium bicarbonate solution and water, the aqueous phase extracted with dichloromethane (3×100 mL), and solvent removed from the extract under reduced pressure. The residue was purified by flash chromatography (rf: 0.48 in 2:1 hexanes:ethyl acetate) to give 4-chloropicolinic acid isopropyl ester (11.0 g, 87% yield). 200.1 (M+1).

Workup

  1. waitAfter a further 30 minutes
  2. customafter a further 15 minutes
  3. extractionthe aqueous phase extracted with dichloromethane (3×100 mL), and solvent
  4. customremoved from the
  5. extractionextract under reduced pressure
  6. customThe residue was purified by flash chromatography (rf: 0.48 in 2:1 hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-92eec345011d469a9571dab7c81ad343
Source dataset
uspto-grants-2013_02
Patent number
US08378108B2

Reaction notes

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