Toluene → 3-Fluoro-4-(2-piperidin-1-ylethoxy)benzoyl chloride hydrochloride

HRID 1434051Notes

Reaction equation

[ClH:1].[F:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:6](O)=[O:7].C1(C)C=CC=CC=1>S(Cl)(Cl)=O>[ClH:1].[F:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH2:14][N:15]1[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1)[C:6]([Cl:1])=[O:7]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 3-fluoro-4-(2-piperidin-1-ylethoxy)benzoic acid hydrochloride (2.0 g) in thionyl chloride (20 ml) was added toluene (20 ml), the solution was stirred for 30 minutes at 100° C., then the reaction solution was concentrated in vacuo to provide 3-fluoro-4-(2-piperidin-1-ylethoxy)benzoyl chloride hydrochloride (2.0 g). To a solution of 2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenylamine (253 mg) in dichloromethane (8 ml) were sequentially added an aqueous solution of 1N sodium hydroxide (4 ml) and 3-fluoro-4-(2-piperidin-1-ylethoxy)benzoyl chloride hydrochloride (400 mg), and the solution was stirred overnight at room temperature. The solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, then the solvent was evaporated in vacuo. Synthesized from the resulting 3-fluoro-N-[2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]-4-(2-piperidin-1-ylethoxy)benzamide (423 mg) according to an analogous synthetic method to Example 337 described below, the title compound (418 mg) was obtained.

Workup

concentrationthe reaction solution was concentrated in vacuo

Sources & evidence

ORD record: ord-0851fd244d9b4f90b78471f90c5374f9
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612114B2

Reaction notes

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