9-Methyl-9-azabicyclo nonane

Trimethyl-9-azabicyclo[3.3.1 ] nonan-30i-ol Methyl 0i,ai-di(2-thienyl)glycollate... 

A mixture of 1.0 g of 6,6,9-trimethyl-9-azabicyclo[3.3.1 ] nonan-3/3-ol, methyl 0i,0i-di-(2-thienyD-glycollate and 30 mg of metallic sodium is heated at 80°C to 90°C for about 2 hours under reduced pressure. After cooling, ether is added to the reaction mixture. The mixture is extracted with 10% hydrochloric acid. The aqueous layer is alkalified with sodium carbonate and reextracted with ethyl acetate. The extract is washed with water, dried and concentrated to dryness. The residue thus obtained is treated with hydrogen chloride by conventional manner. 2.0 g of the 0i,0i-di-(2-thienyl)glycollate of 6,6,9-trimethyl-9-azabicyclo-(3.3.1 ] nonan-3/3-ol hydrochloride are obtained. Yield 83%. 

C3SH52N2O10S 18409-40-0) see Atropine methonitrate e/ido-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine (C9H1JN2 76272-56-5) see Granisetron methyl azidoacetate... 

The reaction of LTMP at 80° with 2,2,6,6-tetramethylcyclohexane (3) to give 4 evidently involves transfer of a 3-methyl of LTMP, since 6 is also formed during the reaction. The minor carbinol (5) of this reaction can be formed in quantitative yield when N-lithio-9-azabicyclo[3.3.1]nonane (7) is used as the base. This base lacks both p-hydrogens and p-methyl groups, but evidently can metalate a methyl group of 3 to form the anion b. The same paper also presents evidence for bridgehead metalation by LTMP. 

Enehydroxylamines (102) are invoked as intermediates in the rearrangement of O-vinyl, acyl or aryl oximes (101) (equation 31). Varlamov and coworkers demonstrated that the heterocyclization of ketoximes (103) with acetylene in snper basic medium and in the presence of metal hydroxides proceeds by a [3,3]-sigmatropic rearrangement of the enehydroxylamine 105 of the corresponding oxime vinyl ethers 104 (equation 32). The unreactivity of 3-methyl-2-azabicyclo[3.3.1]nonan-9-one oxime (106) in the same reaction conditions was explained by its inability to isomerize to the corresponding enehydroxylamine. 

Daly, J. W., Tokuyama, T., Fujiwara, T., Highet, R. J., Karle, I. L. A new class of indolizidine alkaloids from the poison frog, Dendrobates tricolor. X-ray analysis of 8-hydroxy-8-methyl-6-(2 -methylhexylidene)-1-azabicyclo[4.3.0]nonane, J. Am. Chem. Soc. 1980, 102, 830-836. 

The Aae values (at 60 MHz) observed for 3-azabicyclo[3.3.1]nonane and its Af-methyl derivative were 0.08 and 0.67 ppm respectively, a decrease of 0.5-0.6 ppm compared to the Aae values for the corresponding piperidines. On this evidence the conformations 15 and 16 were assigned to these compounds.37... 

New total syntheses9 of azabicyclo[4.2.1]nonanone (10) have now been elaborated. The first synthesis started with 5-azidocyclo-oct-l-ene (7). Reduction and iV-methylation (via the urethane), followed by treatment of the secondary amine with hypobromous acid and with base, gave a mixture of 9-methyl-9-azabicyclo[4.2.1]nonan-2a-ol (8) and its 2/3-isomer (9), contaminated with some azabicyclo[3.3.1]nonane analogue cf. (18). The second synthesis starts with the monoepoxide from cyclo-octa-1,5-diene (11). Treatment with methylamine and... 

The crude 3-(p-nitrobenzenesulfonyl)-3-azabicyclo[3.2.2]nonane (44.0 g, 0.14 mole), 5.0 g alcohol wet Raney nickel, and 400 ml methyl alcohol were charged to an autoclave and reduced at 70°C at 1000 p.s.i. hydrogen pressure until absorption of hydrogen had stopped. The crude reduced product was filtered hot to remove the Raney nickel catalyst. The filtrate was cooled to 20°C and the solid 3-(p-ammobenzenesulfonyl)-3-azabicyclo[3.2.2]nonane was collected by filtration (38.9 g 98% theory), melting point 149°-151°C. 

A solution of l-(phenylmethyleneamino)isatin (1.354 g, 0.0054 mol) and endo-3-amino-9-methyl-9-azabicyclo[3.3.1]nonane (0.832 g, 0.0054 mol) in dry THF (25 ml) under argon was heated to reflux for 5 hours. The solution was cooled and evaporated and the residual traces of THF were azeotropically removed with dichloromethane. The residue was triturated with ether to give the intermediate 2-(benzylidenehydrazino)-a-oxophenyl-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)carboxamide as an orange powder (1.583 g, 73%). 

Trimethyl-9-azabicyclo[3.3.1]nonan-3a-ol Methyl a,a-di(2-thienyl)glycolate... 

Granisetron (Gran C18H24N40 MW 312.19 g/mol CAS-No. 109889-09-0 endo-1-methyl-/V-[9-methyl-9-azabicyclo-[3,3,l]nonane-3-yl]-lH-imidazole-3-carboxamide). 

One of the most popular methods for creating the anatoxin-a skeleton is by transannular cyclization of a suitably substituted cyclooctene. This approach was used in the first synthesis of racemic anatoxin-a (Campbell et al. 1979). They carried out two different methodologies in order to reach the 9-azabicyclo[4.2.1]nonane structure (Scheme 7.3). The 1,5-cyclooctadiene (10) starting compound was transformed into the methyl amine 11 which was treated with hypobromous acid to produce the desired bicycle 12 as a mixture of diastereoisomers in 29% overall yield, with some amount of the azabicyclo[3.2.1] analogue (Bastable etal. 1972). 

Wiseman and Lee (1986) also reached the ketone 14 by a route involving the cyclization of 1,5-cyclooctanediol (16 Scheme 7.4). This transformation involved the Jones oxidation of 16 to give the hemiketal 17, which was transformed into the 9-methyl-9-azabicycle[3.3.1]nonan-l-ol 18 by treatment with methylamine, followed by addition of sulphuric acid (Quinn et al. 1973). This skeleton was reconverted into the 9-azabicyclo[4.2.1]nonane by bromination-reorganisation with pyri-dinium bromide perbromide in hot acetic acid in one direct step (Stjernlof et al. 1989). This constitutes the key step of this synthesis, affording the ketone 14 in 56% yield. 

Ferguson, J.R., Lumbard, K. W., Scheinmann, E, Stachulski, A.V, Stjernlof, E, and Sundell, S. 1995. Efficient new syntheses of (+)- and (-)-anatoxin-a. Revised configuration of resolved 9-methyl-9-azabicyclo[4.2.1]nonan-2-one. Tetrahedron Lett 36, 8867-8870. 

The exo-2-methyl- and ethyl-substituted 3-benzyl-3-azabicyclo[3.3.1]-nonanes were shown to adopt the CC conformation in solution (from 13C-NMR data), while for the exo-2-isopropyl compound the CB conformation is predominant (106). 

In solution the endo-3 and exo-3 substituted compounds 233 and 234 adopt CB and CC conformations, respectively, according to 13C-NMR data (177). A variable temperature l3C-NMR study of 9-methyl-9-azabicyclo-[3.3.1]nonane has shown that the nitrogen inversion barrier is AG1 = 8.1 kcal mol"1 at — 90°C(178). For some other 9-heterobicyclo[3.3.1]nonanes studied using 13C-N M R data, the conformational behavior was shown to be governed by steric interactions (177-180). 

The reduction of higher homologs of tropinone, i.e., 9-methyl-9-azabicyclo[3.3.1]nonan-3-one (pseudopelletierine) and 10-methyl-10-azabicyclo[4.3.1]dccan-8-one (homopseudopelletierine)28 by sodium and ethanol, results in the predominant formation of the equatorial /(-alcohols. 

The pseudopelletierine analogs 9-methyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-one and 9-methyl-3-thia-9-azabicyclo[3.3.1]nonan-7-one were reduced stereospecifically with sodium and pen-tanol to give the corresponding equatorial /(-alcohols in 80% and 75% yield, respectively. 

---