Phosphorus oxychloride → 4-Chloro-6-(2,6-diethyl-phenyl)-nicotinic acid methyl ester

HRID 251593Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:22])[C:4]1[C:9](OC)=[CH:8][C:7]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:6][CH:5]=1.O=P(Cl)(Cl)[Cl:25]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:22])[C:4]1[C:9]([Cl:25])=[CH:8][C:7]([C:12]2[C:17]([CH2:18][CH3:19])=[CH:16][CH:15]=[CH:14][C:13]=2[CH2:20][CH3:21])=[N:6][CH:5]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6-(2,6-diethyl-phenyl)-4-methoxy-nicotinic acid methyl ester (4.0 g, 13.4 mmol), DMF (10 mL) and POCl3 (10 mL) is heated at 80° C. overnight. The volatile material is removed in vacuo. Ice water, NaHCO3 and hexane (50 mL) are added to the residue. The organic layer is separated and the aqueous layer is extracted with hexane (2×30 mL). The combined organic layer is washed with water, dried, and concentrated. The crude product is purified by silica gel chromatography (1% MeOH in CH2Cl2) to give 4-chloro-6-(2,6-diethyl-phenyl)-nicotinic acid methyl ester. 1H NMR (CDCl3) 9.12 (s, 1H), 7.40 (s, 1H), 7.30 (d, 1H), 7.15 (d, 2H), 4.00 (s, 3H), 2.30 (q, 4H), 1.05 (t, 6H).

Workup

customThe volatile material is removed in vacuo
additionIce water, NaHCO3 and hexane (50 mL) are added to the residue
customThe organic layer is separated
extractionthe aqueous layer is extracted with hexane (2×30 mL)
washThe combined organic layer is washed with water
customdried
concentrationconcentrated
customThe crude product is purified by silica gel chromatography (1% MeOH in CH2Cl2)

Sources & evidence

ORD record: ord-361b770c922645ac9903c99da7066a29
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863454B2

Reaction notes

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