Preparation and crystal structure of 6-acetyl-1-iodocodeine

Abstract

N -[ g-(Dimethylamino)phenyl]-a-(2-amino-3-cyano-5-pyr-aziny1)nitrone (5). To a suspension of 2.63 g (10.6 mmol) of the pyridinium salt 4 and 1.64 g (11.0 mmol) ofp-dimethylaminonitrosobenzene in 50 mL of ethanol was added 8.33 g (60.4 mmol) of potassium carbonate in 30 mL of water. The reaction mixture became homogeneous, changed in color from green to brown, and the orange-brown nitrone started to separate. After 30 min of stirring at room temperature followed by ice cooling, the mixture was filtered and the collected solid was washed with water followed by ethanol and then ether and air-dried: yield 2.86 g (96%) of a dull orange powder, mp 219-222 OC (dec). Recrystallization from a large volume of acetonitrile (Norite) gave dark-orange needles: mp 227-228 OC (dec); NMR (Me2SO) F 2.95 (s, 6), 6.68 (d, 2), 7.72 (m, 4) (2 Ar protons + -NH2), 8.15 (s, l), 9.92 (9, 1); UV A , , ,(acetonitrile) (log

Codeine dihydrogen phosphate hemihydrate

“…morphine monohydrate (Bye, 1976) and morphine derivatives, such as morphine monohydrate (Bye, 1976), salts (Mackay & Hodgkin, 1955;Gylbert, 1973;Wongweichintana et al, 1984;Lutz & Spek, 1998) and derivatives (e.g. Canfield et al, 1979;Deschamps et al, 1996;Gathergood et al, 2003;Balchin et al, 2004) of morphine, the free base form of codeine (Canfield et al, 1987), codeine monohydrate (Bel'skii et al, 1988), codeine hydrobromide dihydrate (Kartha et al, 1962) and codeine derivatives (Grant et al, 1993;Kolev et al, 2006;Liebman et al, 1978). Using the nomenclature commonly applied to opiates, the mean planes defined by the rings A/B/C and D/E (see the scheme) form angles of 89.36 (5) and 88.66 (5) in the two independent cations of (I).…”

Synthesis of [15, 16‐3H] beta‐funaltrexamine

“…Given the functional group limitations of the target molecule though, only an aromatic iodo‐derivative of 1 serving as a substrate for a chemoselective aromatic tritium dehalogenation would be a possible approach. However, it is well known that direct iodination of morphine is problematic and only accomplished by a multi‐step protection–deprotection scheme . For that reason, it made more sense to simply start the synthesis from high specific activity [15, 16‐ 3 H] naltrexone and submit it to the two‐step reductive amination–acylation process used to synthesize unlabeled beta‐funaltrexamine.…”

Tritiated dihydro compounds employed as radioligand surrogates

“…A very clever solution to the morphine tritiation problem posed by the olefin was that of Seltzman and Research Triangle Institute co‐workers cited earlier . These investigators first prepared 1‐iodomorphine ( 8 ) and then protected its 6‐position allylic alcohol as the tert ‐butyldimethylsilyl ether. This bulky appendage sterically hindered the proximate olefin from catalytic tritiation, allowing regioselective tritium dehalogenation of the 1‐position iodine to afford (after deprotection) [1‐ 3 H]morphine at 21.4 Ci/mmol.…”