Isopropanol → 6-Chloro-4-isopropoxy-2-methyl-nicotinic acid isopropyl ester

HRID 251646Notes

Reaction equation

HRID 251646 reaction equation
[CH:1]([OH:4])([CH3:3])[CH3:2].[H-].[Na+].[CH:7]([O:10][C:11](=[O:21])[C:12]1[C:17](Cl)=[CH:16][C:15]([Cl:19])=[N:14][C:13]=1[CH3:20])([CH3:9])[CH3:8]>C1COCC1.[Cu]I>[CH:7]([O:10][C:11](=[O:21])[C:12]1[C:17]([O:4][CH:1]([CH3:3])[CH3:2])=[CH:16][C:15]([Cl:19])=[N:14][C:13]=1[CH3:20])([CH3:9])[CH3:8]

Participants

6

Reactant 3

HCID 3776IsopropanolHCID 24758Sodium hydrideHCID 86593990Isopropyl 4,6-dichloro-2-methylnicotinate

Product 1

HCID 865939896-Chloro-4-isopropoxy-2-methyl-nicotinic acid isopropyl ester

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Anhydrous isopropanol (1.5 mL, 20 mmol) is added to a suspension of NaH (1.5 g of 60% dispersion in mineral oil, 37 mmol) in THF (90 mL) at 0° C. and the mixture is stirred for 30 minutes at ambient temperature. To this is added a solution of 4,6-dichloro-2-methyl-nicotinic acid isopropyl ester (4.6 g, 19 mmol) in THF (10 mL) and CuI (178 mg, 0.94 mmol) The mixture is refluxed for 1 hour, cooled to room temperature, and poured into water-ice mixture. The layers are separated and the aqueous layer is extracted with EtOAc. The combined organic layers are dried (MgSO4) and concentrated in vacuo. The residue is purified by flash chromatography (elution with Hex/EtOAc 61) to yield 6-chloro-4-isopropoxy-2-methyl-nicotinic acid isopropyl ester as a pale yellow oil. 1H NMR (CDCl3) 6.65 (s, 1H), 5.24 (m, 1H), 4.60 (m, 1H), 2.41 (s, 3H), 1.28 (d, 12H).

Workup

  1. temperatureis refluxed for 1 hour
  2. temperaturecooled to room temperature
  3. customThe layers are separated
  4. extractionthe aqueous layer is extracted with EtOAc
  5. dry with materialThe combined organic layers are dried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash chromatography (elution with Hex/EtOAc 61)

Sources & evidence

ORD record
ord-395ba2b1a4b54da4b817de1a32c3d3c8
Source dataset
uspto-grants-2011_01
Patent number
US07863454B2

Reaction notes

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