1 + /- - -4-Methyl-3-phenylperhydropyrido oxazin

A single stereoisomer of 4-methyl-3-phenylperhydropyrido[2,l-c][l,4]oxa-zine 279, containing a fused bicycle, was obtained by the cyclization of l-(2-hydroxyethyl)-2-piperidinemethanol 235 in CH2CI2 on the action of cone. H2SO4 (97JHC1813). Similarly, l-phenylperhydropyrido[2,l-c][l,4] oxazine 281 was obtained from l-(2-hydroxyethyl)-2-[(phenyl)hydroxy-methyljpiperidine 280. 

Treatment of 3-phenylperhydropyrido[ 1,2-/ 1,3 oxazin-l -one with LAH gave a 1 9.5 mixture of 3-phenylphenylper-hydropyrido[l,2-c][l,3]oxazine and l-methyl-2-(2-phenyl-2-hydroxyethyl)piperidine <20050BC520>. Reduction of ds- >,4a- I-/ra .v-8-H-3-incthyl-8-pentyIperhydropyrido[ 1 1,3 oxazin-6-onc with NaBH4 at room temperature... 

Reduction of 6,8-diazabicyclo[3,2,l]oct-6-enes 411, prepared from 410 with alkyl- or phenyllithium, with NaBH3CN gave 1-amino-l-substituted 4-phenylperhydropyrido[2,l-f][l,4]oxazines 412 (Equation 76) <1996JOC6700>. The 1-methyl derivative of 412 (R1 = Me) was accompanied by 10% of the C-l epimer. A 3 7 mixture of 4-phenylperhy-dropyrido[2,l-r ][l,4]oxazin-l-one was obtained from 410 by treatment with HC1 in the presence of Si02, then with Zn(BH4)2 <2003JOC1401>. 

The 3-methyl- and 3-phenylperhydropyrido[l,2-c][l,3]oxazines all adopt the trans-fused conformation (274—277).135 The two 4-methyl derivatives 278 and 279 also adopt the trans conformation (Jgem — 7.8 Hz in both isomers) but 279 shows an enhanced Aae (0.87 ppm) (cf. 0.59 ppm in 278) which cannot be due to changes in cis trans conformational equilibria.279... 

Cyclization of methyl 4-(c/s-3,5-H-2-oxomorpholin-5-yl)butyrate in boiling toluene provided c/s-4,9a-H-4-phenylperhydropyrido[2,l-c][l,4]ox-azine-3,6-dione [95H(41)1931], Heating l,4-oxazin-2-one 163 afforded [l,4]oxazino[4,3-a]quinoline-4,6-dione 164 (94IZV299, 94JFC119). The reaction of carboxylic acid 165 with l.l -carbonyldiimidazole in the presence of 4-methylmorpholine afforded pyrido[2,l-c][l,4]oxazin-4-one (61)... 

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