(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 251487Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 251487
[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

Komponenten

5

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-a739371959384828a889782a7d27947f
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863449B2

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