Triethylamine → 2-Methyl-6-trifluoromethylnicotinic acid 4-oxobicyclo[3.2.1]oct-2-en-2-yl ester

HRID 24294Notes

Reaction equation

[CH2:1]=[C:2]1[CH:8]2[CH2:9][CH:5]([CH2:6][CH2:7]2)[C:4](=[O:10])[O:3]1.C(N(CC)CC)C.[C-]#N.[K+].[CH3:21][C:22]1[N:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[CH:27][C:23]=1[C:24](Cl)=[O:25]>C(#N)C>[O:10]=[C:4]1[CH:5]2[CH2:9][CH:8]([CH2:7][CH2:6]2)[C:2]([O:3][C:24](=[O:25])[C:23]2[CH:27]=[CH:28][C:29]([C:31]([F:34])([F:32])[F:33])=[N:30][C:22]=2[CH3:21])=[CH:1]1

Participants

Conditions

Temperature: 20 °C

Procedure

2.07 g (0.015 mol) of distilled 4-methylene-3-oxabicyclo[3.2.1]octan-2-one and 3.34 g (0.033 mol) of triethylamine are stirred for 2.5 hours at a temperature of 60° C. in 50 ml of acetonitrile in the presence of 98 mg (1.5 mmol) of potassium cyanide. Cooling to a temperature of 20° C. is then carried out and 2.35 g (0.11 mol) of 2-methyl-6-trifluoromethyl-nicotinoyl chloride, freshly prepared according to WO 00/15615, dissolved in a small amount of acetonitrile are added. The 2-methyl-6-trifluoromethylnicotinic acid 4-oxobicyclo[3.2.1]oct-2-en-2-yl ester (known from WO 00/15615) obtained in situ as intermediate is fully converted within a period of 3.5 hours (monitoring by thin-layer chromatography). The reaction mixture is then acidified with dilute hydrochloric acid and extracted with ethyl acetate against water at a pH value of 2, dried over Na2SO4 and concentrated by evaporation. The product is purified by means of column chromatography (eluant: ethyl acetate/hexane 4:1) to yield 3.16 g of 90% 4-hydroxy-3-(2-methyl-6-trifluoromethylpyridine-3-carbonyl)-bicyclo[3.2.1]oct-3-en-2-one (58.3% based on the 4-methylene-3-oxabicyclo[3.2.1]octan-2-one used or 83.3% based on the 2-methyl-6-trifluoromethylnicotinoyl chloride used).

Workup

additionare added

Sources & evidence

ORD record: ord-0438a32ec491409b92ddd31bbb26d836
Source dataset: uspto-grants-2005_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06855831B2

Reaction notes

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