Water → 2-(1-Ethylpropyl)-6-methoxyisonicotinic acid methyl ester

HRID 245079Notes

Reaction equation

HRID 245079 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[N:7]=[C:6](Cl)[CH:5]=1.[Br-].[CH3:15][CH2:16][CH:17]([Zn+])[CH2:18][CH3:19].O>C1COCC1>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[N:7]=[C:6]([CH:17]([CH2:18][CH3:19])[CH2:16][CH3:15])[CH:5]=1

Participants

5

Reactant 3

HCID 962WaterHCID 13339618Methyl 2-chloro-6-methoxyisonicotinateHCID 178456109HCID 178456109, compound

Product 1

HCID 670268752-(1-Ethylpropyl)-6-methoxyisonicotinic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
85 °C

Procedure

Under argon, Pd(dppf) (3.04 g, 4 mmol) is added to a solution of 2-chloro-6-methoxy-isonicotinic acid methyl ester (50 g, 0.248 mol) in THF (100 mL). A 0.5 M solution of 3-pentylzincbromide in THF (550 mL) is added via dropping funnel. Upon complete addition, the mixture is heated to 85° C. for 18 h before it is cooled to rt. Water (5 mL) is added and the mixture is concentrated. The crude product is purified by filtration over silica gel (350 g) using heptane:EA 7:3 to give 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid methyl ester (53 g) as a pale yellow oil; 1H NMR (CDCl3): δ0.79 (t, J=7.5 Hz, 6H), 1.63-1.81 (m, 4H), 2.47-2.56 (m, 1H), 3.94 (s, 3H), 3.96 (s, 3H), 7.12 (d, J=1.0 Hz, 1H), 7.23 (d, J=1.0 Hz, 1H).

Workup

  1. additionUpon complete addition
  2. temperatureis cooled to rt
  3. concentrationthe mixture is concentrated
  4. filtrationThe crude product is purified by filtration over silica gel (350 g)

Sources & evidence

ORD record
ord-6afaebd5f60645648aa23aa8fecedf76
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

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