Reaktion #684568

Reaktionsgleichung

1-(2'-Amino-5'-bromo-4'-methoxybenzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline dihydrochloride

1-(2'-Amino-5'-bromo-4'-methoxybenzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline Dihydrochloride

sodium nitrite

→

9-bromo-2,10-dimethoxy-1-hydroxyaporphine hydrochloride

Ausbeute 43.0%

9-Bromo-2,10-dimethoxy-1-hydroxyaporphine Hydrochloride

Ausbeute 43.0%

Lösungsmittel

sulfuric acid

acetic acid

water

chloroform

Reaktionsbedingungen

Aufarbeitung

1. 1
   Filtrationfiltered through a short column of silica gel (3 g)
2. 2
   Wascheneluting with chloroform-methanol (97:3, 200 ml)
3. 3
   SonstigeRemoval of solvent
4. 4
   workup.WAITleft a brown gum which
5. 5
   workup.ADDITIONwas treated with ethanol (6 ml) saturated with hydrogen chloride gas
6. 6
   SonstigeSolvents were removed
7. 7
   FiltrationFiltration
8. 8
   Sonstigegave the crude aporphine hydrochloride as a pale brown solid (318 mg)
9. 9
   SonstigeRecrystallization from methanol

Vorschrift

General procedure as described in Example III. 1-(2'-Amino-5'-bromo-4'-methoxybenzyl)-2-methyl-6-methoxy-7-hydroxy-1,2,3,4-tetrahydroisoquinoline dihydrochloride (4c) (448 mg) in 20% sulfuric acid (4 ml) and glacial acetic acid (4 ml) was diazotized using sodium nitrite (77 mg) in water (0.75 ml), and the subsequent Pschorr cyclization used copper powder (450 mg) in the usual manner. The crude product was a brown gum (353 mg) which was dissolved in chloroform and filtered through a short column of silica gel (3 g), eluting with chloroform-methanol (97:3, 200 ml). Removal of solvent left a brown gum which was treated with ethanol (6 ml) saturated with hydrogen chloride gas. Solvents were removed and the residue was stirred overnight with ether (30 ml). Filtration gave the crude aporphine hydrochloride as a pale brown solid (318 mg). Recrystallization from methanol gave 9-bromo-2,10-dimethoxy-1-hydroxyaporphine hydrochloride (5c) as a dull yellow crystalline solid (171 mg, 43%), mp 237°-240° (dec). Three recrystallizations from methanol pale yellow-greenish needles, mp 241°-243° (dec); λmaxKBr 2.75-3.30 μ (broad O--H and N--H); λmaxEtOH (c) 219 (39,415), 269.5 (13,710), 279.5 (16,970), 305 sh (13,195), and 311 nm (13,540); mass spectrum m/e 390, 389 (M+ - HCl), 388 (M+ - HCl-1), 387, 376, 374, 348, and 346.

Quelle