(3-Methoxyphenyl)boronic acid → ethyl 3-(2-(3-methoxyphenyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

HRID 251487ノート

反応式

HRID 251487 の反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.Cl.[N:13]1([CH:28]2[CH2:34][CH:33]3[N:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH:30]([CH2:31][CH2:32]3)[CH2:29]2)[CH2:18][CH2:17][C:16]2([C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21][NH:20][CH2:19]2)[CH2:15][CH2:14]1>C(Cl)Cl.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:20]2[CH2:19][C:16]3([CH2:17][CH2:18][N:13]([CH:28]4[CH2:29][CH:30]5[N:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[CH:33]([CH2:32][CH2:31]5)[CH2:34]4)[CH2:14][CH2:15]3)[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:21]2)[CH:6]=[CH:7][CH:8]=1

参加物

5

反応物 2

HCID 2734370(3-Methoxyphenyl)boronic acidHCID 86609340Ethyl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate hydrochloride

生成物 1

HCID 58089606ethyl 3-(2-(3-methoxyphenyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

実験手順

A suspension of 3-methoxyphenylboronic acid (30 mg, 0.2 mmol), Cu(OAc)2H2O (2 mg, 5 mol %), 3 Å molecular sieves (75 mg) in 1 mL of CH2Cl2 were stirred at room temperature for 5 min. Ethyl 3-(2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate hydrochloride 5c (42 mg, 0.1 mmol) was added to the reaction and mixture was stirred at room temperature for 24 h. The reaction was diluted with methanol, filtered and subjected to reverse-phase HPLC purification (2-50% CH3CN—H2O gradient, with 0.05% TFA, 15 min) to give pure ethyl 3-(2-(3-methoxyphenyl)-2,3-dihydro -1H-spiro[isoquinoline-4,4′-piperidine]-1′-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate. LC-MS: m/z [M+H]+ 490.0, retention time 2.61 min (10-90% CH3CN—H2O gradient, with 0.05% TFA, 5 min).

後処理

  1. stirringwas stirred at room temperature for 24 h
  2. filtrationfiltered
  3. customsubjected to reverse-phase HPLC purification (2-50% CH3CN—H2O gradient, with 0.05% TFA, 15 min)

出典と根拠

ORDレコード
ord-a739371959384828a889782a7d27947f
出典データセット
uspto-grants-2011_01
特許番号
US07863449B2

反応ノート

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