Sodium Hydroxide → [3-Fluoro-4-(2-piperidin-1-ylethoxy)benzyl][2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]amine

HRID 1950240Notes

Reaction equation

HRID 1950240 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH2:9][CH:8]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[NH2:19])[CH2:7][CH2:6]2.[OH-].[Na+].Cl.[F:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)[C:27](Cl)=O>ClCCl>[F:23][C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][C:32]=1[O:33][CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1)[CH2:27][NH:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH:8]1[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[CH2:9]1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 230871263-Fluoro-4-(2-piperidin-1-ylethoxy)benzoyl chloride hydrochlorideHCID 230875022-(6-Methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenylamine

Product 1

HCID 57933961[3-Fluoro-4-(2-piperidin-1-ylethoxy)benzyl][2-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)phenyl]amineYield 85.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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

  1. extractionThe solution was extracted with ethyl acetate
  2. washsequentially washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated in vacuo
  5. customSynthesized 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)

Sources & evidence

ORD record
ord-4b5e214870be4b86a38b78a4333278b6
Source dataset
uspto-grants-2013_03
Patent number
US08399520B2

Reaction notes

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