Quinoline → 1-[4-(7-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperidin-1-yl]-ethanone

HRID 501327Notes

Reaction equation

[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]2[C:11]3[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([F:25])([F:24])[F:23])[C:12]=3[S:13][C:14]=2C(O)=O)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].N1C2C(=CC=CC=2)C=CC=1>C(OCC)(=O)C>[F:25][C:22]([F:23])([F:24])[C:18]1[C:12]2[S:13][CH:14]=[C:10]([CH:7]3[CH2:6][CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8]3)[C:11]=2[CH:21]=[CH:20][CH:19]=1

Participants

Conditions

Temperature: 200 °C

Procedure

A mixture of 3-(1-acetyl-piperidin-4-yl)-7-trifluoromethyl-benzo[b]thiophene-2-carboxylic acid (4.13 g, 1.1 mmol), Cu powder (0.706 g, 11.1 mmol), and quinoline (20 mL) was heated to 200° C. under nitrogen. After 10 min, no gas evolution was observed and the reaction cooled at room temperature. The mixture was diluted with ethyl acetate (100 mL), filtered through a Celite bed and the filtrate washed with 1 N HCl (2×100 mL), 5% aqueous potassium carbonate (100 mL), water (100 mL), and brine (100 mL) successively. The organics were dried over magnesium sulfate, filtered, and concentrated to give an amber oil. The oil was chromatographed on silica, eluting with 10% methanol/ethyl acetate to afford 2.69 g (74%) of the desired product as a tan solid.

Workup

temperaturethe reaction cooled at room temperature
filtrationfiltered through a Celite bed
washthe filtrate washed with 1 N HCl (2×100 mL), 5% aqueous potassium carbonate (100 mL), water (100 mL), and brine (100 mL) successively
dry with materialThe organics were dried over magnesium sulfate
filtrationfiltered
concentrationconcentrated
customto give an amber oil
customThe oil was chromatographed on silica
washeluting with 10% methanol/ethyl acetate

Sources & evidence

ORD record: ord-7ade7fea02c1462aba4f77f659c9ef32
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772252B2

Reaction notes

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