HCID 21447066, compound → HCID 21447047, compound

HRID 597386Notes

Reaction equation

HRID 597386 reaction equation
[ClH:1].Cl.N[C:4]1[CH:24]=[C:23]([O:25][CH3:26])[C:22]([Br:27])=[CH:21][C:5]=1[CH2:6][CH:7]1[C:16]2[C:11](=[CH:12][C:13]([O:18][CH3:19])=[C:14]([OH:17])[CH:15]=2)[CH2:10][CH2:9][N:8]1[CH3:20].N([O-])=O.[Na+]>S(=O)(=O)(O)O.C(O)(=O)C.O.C(Cl)(Cl)Cl.[Cu]>[ClH:1].[Br:27][C:22]1[CH:21]=[C:5]2[C:4](=[CH:24][C:23]=1[O:25][CH3:26])[C:15]1=[C:16]3[CH:7]([N:8]([CH3:20])[CH2:9][CH2:10][C:11]3=[CH:12][C:13]([O:18][CH3:19])=[C:14]1[OH:17])[CH2:6]2

Participants

8

Reactant 2

HCID 21447066HCID 21447066, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 21447047HCID 21447047, compoundYield 43%

Reagents, catalysts & solvents 5

HCID 23978CopperCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 1118Sulfuric AcidSolventHCID 6212ChloroformSolvent

Procedure

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.

Workup

  1. filtrationfiltered through a short column of silica gel (3 g)
  2. washeluting with chloroform-methanol (97:3, 200 ml)
  3. customRemoval of solvent
  4. waitleft a brown gum which
  5. additionwas treated with ethanol (6 ml) saturated with hydrogen chloride gas
  6. customSolvents were removed
  7. filtrationFiltration
  8. customgave the crude aporphine hydrochloride as a pale brown solid (318 mg)
  9. customRecrystallization from methanol

Sources & evidence

ORD record
ord-094d481c28474296a1e73b7ea65c22c9
Source dataset
uspto-grants-1977_03
Patent number
US04013664

Reaction notes

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