Ammonium Chloride → N-[5-methoxy-2-(6-methoxynaphthalen-2-yl)phenyl]-4-(2-piperidin-1-ylethoxy)benz amide

HRID 1433942Notes

Reaction equation

HRID 1433942 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:20][CH3:21])[CH:16]=3)[CH:11]=2)=[C:7]([NH2:9])[CH:8]=1.C(N(CC)C(C)C)(C)C.Cl.[N:32]1([CH2:38][CH2:39][O:40][C:41]2[CH:49]=[CH:48][C:44]([C:45](Cl)=[O:46])=[CH:43][CH:42]=2)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.[Cl-].[NH4+]>O1CCCC1.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:20][CH3:21])[CH:16]=3)[CH:11]=2)=[C:7]([NH:9][C:45](=[O:46])[C:44]2[CH:43]=[CH:42][C:41]([O:40][CH2:39][CH2:38][N:32]3[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]3)=[CH:49][CH:48]=2)[CH:8]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 161119224-(2-Piperidin-1-ylethoxy)benzoyl chloride hydrochlorideHCID 230875115-Methoxy-2-(6-methoxynaphthalen-2-yl)phenylamine

Product 1

HCID 23087459N-[5-methoxy-2-(6-methoxynaphthalen-2-yl)phenyl]-4-(2-piperidin-1-ylethoxy)benz amideYield 46.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 5-methoxy-2-(6-methoxynaphthalen-2-yl)phenylamine (275 mg) in tetrahydrofuran (8 ml) were sequentially added triethylamine (1.3 ml), N,N-diisopropylethylamine (1 ml) and 4-(2-piperidine-1-ylethoxy)benzoyl chloride hydrochloride (1.1 g), and the solution was stirred for 2 days at 60° C. A saturated aqueous solution of ammonium chloride was added thereto, the solution was extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system) to provide N-[5-methoxy-2-(6-methoxynaphthalen-2-yl)phenyl]-4-(2-piperidin-1-ylethoxy)benz amide (234 mg). To a suspension of lithium aluminum hydride (50 mg) in tetrahydrofuran (4 ml) was added aluminum chloride (176 mg) on an ice bath under a nitrogen atmosphere, the solution was stirred for 20 minutes at room temperature, N-[5-methoxy-2-(6-methoxynaphthalen-2-yl)phenyl]-4-(2-piperidin-1-ylethoxy)benzamide (226 mg) was added thereto followed by stirring overnight at room temperature. Obtained by sequentially adding tetrahydrofuran and aqueous ammonia, the suspension was filtered through celite pad, and the filtrate was concentrated in vacuo. The residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (213 mg).

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. customThe residue was purified by NH silica gel column chromatography (hexane-ethyl acetate system)

Sources & evidence

ORD record
ord-bcdf8ed0060942e4b2b2183b240f90a0
Source dataset
uspto-grants-2009_11
Patent number
US07612114B2

Reaction notes

Loading…