ONE-POT SYNTHESIS OF PAPAVERINE HYDROCHLORIDE
1299
An aqueous solution of sodium hydroxide (276 g,
FUNDING
6.9 mol, 0.02 M) was then added, and the mixture was
stirred for 30 min and allowed to settle down, the
organic phase was separated, and the aqueous phase
was extracted once with xylene and combined with the
organic phase. The purity of 5 was 98%.
We thank the Engineering Research Center for the Im-
provement & Industrialization of Pharmaceutical Processes
for financial support.
CONFLICT OF INTEREST
The authors declare no conflict of interest.
SUPPLEMENTARY MATERIALS
1-[(3,4-Dimethoxyphenyl)methyl]-6,7-dime-
thoxyisoquinoline (6). The organic phase obtained in
the previous step was transferred to a 5-L reaction
flask, Raney nickel (260 g, 3.04 mol) was added, and
the mixture was heated at 130°C for 8 h; compound 5
was completely converted (according to HPLC). The
amount of by-product 12 was approximately 30%;
when the mixture was further heated at that tempera-
ture for 20 h, the amount of 12 decreased to 3.64%.
The purity of 6 was 92.56%. Finally, the catalyst was
filtered off.
Supplementary materials are available for this article at
sible for authorized users.
REFERENCES
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1-[(3,4-Dimethoxyphenyl)methyl]-6,7-dime-
thoxyisoquinoline hydrochloride (1). The organic
phase obtained in the previous step was evaporated to
dryness. Absolute ethanol (2.04 L) was added,
36% hydrochloric acid (121.94 g, 1.2 mol) was then
added at room temperature, and the mixture was stirred
for 1 h. The solid product was filtered off; it had
a purity of 99%. Crude 1 and pure water (0.265 L)
were placed in a 3-L reactor and heated under reflux
for 20 min. Absolute ethanol (2.04 L) was slowly
added over a period of 30 min to the clear solution.
Crystal seeds (0.1 g) were added to the solution, and
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1H NMR spectrum (600 MHz, CDCl3), δ, ppm: 8.26 d
(1H, J = 6.5 Hz), 7.88 d (1H, J = 6.5 Hz), 7.63 s (1H),
7.24 d (1H, J = 2.0 Hz), 6.93 d.d (1H, J = 8.2, 2.0 Hz),
6.75 d (1H, J = 8.3 Hz), 4.99 s (2H), 4.11 s (3H), 4.04 s
(3H), 3.85 s (3H), 3.80 s (3H). 13C NMR spectrum
(151 MHz, CDCl3), δC, ppm: 157.00, 154.09, 152.59,
149.52, 148.38, 136.92, 129.33, 128.04, 122.52,
121.54, 120.81, 112.54, 111.33, 106.02, 104.96, 56.88,
56.55, 56.31, 55.87, 36.52. Mass spectrum: m/z 339.1
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 56 No. 7 2020