Trifluoroacetic acid → Ethyl 6-(4-fluorobenzyl)-4-hydroxy-5-oxo-5,6,7,8-tetrahydro-2,6-naphthyridine-1-carboxylate

HRID 1817301Notes

Reaction equation

C(O[C:6]1[O:10][C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8][CH:7]=1)CCC.[F:16][C:17]1[CH:30]=[CH:29][C:20]([CH2:21][N:22]2[CH2:27][CH2:26][CH:25]=[CH:24][C:23]2=[O:28])=[CH:19][CH:18]=1.FC(F)(F)C(O)=O>CCOCC>[F:16][C:17]1[CH:18]=[CH:19][C:20]([CH2:21][N:22]2[CH2:27][CH2:26][C:25]3[C:9]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8][CH:7]=[C:6]([OH:10])[C:24]=3[C:23]2=[O:28])=[CH:29][CH:30]=1

Participants

Conditions

Temperature: 130 °C

Procedure

In a heavy walled round bottom flask with screw top were combined ethyl 5-butoxy-1,3-oxazole-2-carboxylate (2.53 g, 11.88 mmol) and 1-(4-fluorobenzyl)-5,6-dihydropyridin-2-(1H)-one (1.22 g, 5.94 mmol; see Example 1, Step 3) and trifluoroacetic acid (0.46 mL, 5.94 mmol). The vessel was sealed and placed in an oil bath heated to 130° C. The reaction mixture was stirred for 3 days. The dark brown reaction mixture was cooled and a crystalline precipitate formed. The mixture was diluted with ether and the solids collected by filtration and washed with ether to give the product as tan shiny plates. Further product can be obtained by evaporating the mother liquor, adding more trifluoroacetic acid and re-heating the mixture.

Workup

customIn a heavy walled round bottom flask with screw top were combined
customThe vessel was sealed
customplaced in an oil bath
temperatureThe dark brown reaction mixture was cooled
customa crystalline precipitate formed
filtrationthe solids collected by filtration
washwashed with ether
customto give the product as tan shiny plates
customFurther product can be obtained
customby evaporating the mother liquor
additionadding more trifluoroacetic acid
temperaturere-heating the mixture

Sources & evidence

ORD record: ord-0ce00a3796854952bb87784b3e95aed3
Source dataset: uspto-grants-2009_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07598264B2

Reaction notes

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