The
Claisen-Schmidt condensation between 3-(methoxymethoxy)benzaldehyde [13709-05-2] (1) and
cyclohexanone (2) afforded
CID:54364197 (3).
Michael addition of
dimethylamine leads the aminoketone, i.e. 2-[dimethylamino-[3-(methoxymethoxy)phenyl]methyl]cyclohexan-1-one,
CID21518320. Reduction of the ketone proceeds stereospecifically to afford the cis aminoalcohol [51356-58-2] (4). Mild hydrolysis of the product gives the free phenol ciramadol (5).
^Preston KL, Bigelow GE, Liebson IA (March 1987). "Comparative evaluation of morphine, pentazocine and ciramadol in postaddicts". The Journal of Pharmacology and Experimental Therapeutics. 240 (3): 900–10.
PMID3559982.
^Romagnoli A, Keats AS (1986). "Low ceiling respiratory depression by ciramadol". International Journal of Clinical Pharmacology Research. 6 (6): 451–5.
PMID3100462.
^Downing JW, Brock-Utne JG, Holloway AM (December 1983). "Ciramadol--a new synthetic analgesic. A double-blind comparison with oral codeine for postoperative pain relief". South African Medical Journal = Suid-Afrikaanse Tydskrif vir Geneeskunde. 64 (25): 978–82.
PMID6359486.
^Stambaugh JE, McAdams J (February 1987). "Comparison of the analgesic efficacy and safety oral ciramadol, codeine, and placebo in patients with chronic cancer pain". Journal of Clinical Pharmacology. 27 (2): 162–6.
doi:
10.1002/j.1552-4604.1987.tb02178.x.
PMID3680568.
S2CID21229861.
^Yardley, J. P.; Fletcher, H.; Russell, P. B. (1978). "A potent benzylamine analgesic:(−)cis-2(α-dimethylamino-m-hydroxybenzyl)cyclohexanol". Experientia 34(9): 1124–1125. doi:10.1007/BF01922905.