F 4-Methylpiperidine

Methyl-1 -phenylethyl)-4-(2-propynyloxy)benzene, 3754 /V-(3-Methylpheny) )-2-nitrobenzimidyl chloride, 3634 Methylphosphine, 0495 f 1-Methylpiperidine, 2517 f 2-Methylpiperidine, 2518 f 3-Methylpiperidine, 2519 f 4-Methylpiperidine, 2520... 

In the first series (see Scheme 2) lythrine (1) was transformed to 7V-methyl-piperidine (44). The optical rotation was —31° in 43 and + 31° in the corresponding derivative of vertine. The plain positive ORD curve of the O-methyl derivative of the latter compound corresponded to those of D-(-h)-coniine and D-(-f-)-2-methylpiperidine. 

Hydrolysis of the ethyl ester proceeded smoothly using hydrochloric acid in acetic acid to give carboxylic acid 69 in 88% yield (Scheme 4.9). Previously, amines were allowed to react with the carboxylic acid core in hot DMSO to deliver the C7 products however, the difluoroborate 70, derived from the carboxylic acid 69, greatly increased the reactivity of the C7 position. Consequently, the displacement of the C7-F with amines was accomplished at lower temperature (Baker et al., 2004 Cecchetti et al., 1996 Domalaga et al., 1993 Ellsworth et al., 2005a,b Hu et al., 2003). In this event, the carboxylic acid was allowed to react with boron trifluoride to deliver difluroboronate 70 in excellent yield. The thus afforded borate ester reacted with A -methylpiperidine in DMSO in the presence of triethylamine at ambient temperature to furnish ( —)-ofloxacin (1, levofloxacin) in 56% yield. 

A useful practical method for the preparation of aroyl fluorides 1 and arenesulfonyl fluorides 2 by reaction of the zinc(II) fluoride/pyridine system with the corresponding chlorides has been described.50 Replacement of zinc(II) fluoride by potassium fluoride, or of pyridine by other tertiary amines (Et3N or l-methylpiperidin-2-one) or by other solvents (DMSO, DMF, MeCN, or THF) did not give satisfactory results. The exclusive effectiveness of pyridine is presumably due to its ability to weaken the Zn — F linkage by appropriate coordination to the zinc atom.50... 

PhCD2NH2,40,42 as well as the temperature independence of the Ap/f, for CD3M f and (CD3)2NH2,52 Perrin and coworkers reinvestigated these and other secondary IEs.30,31 The amines studied were methylamine (16-do,1,2,3), benzylamine (18-d), N,A -dimethy 1 ani 1 ine (19-d3), 1-benzyl-4-methylpiperidine (20-d3), pyrrolizidine (21-d), N-methy 1 norborny 1 amine (22-d2), and A -benzyl-norbornylamine (23-d). The NMR titration method [Equation (19)], which gives highly accurate results, was applied to the reporter H depicted in boldface on the molecular structures. The results are presented in Table 5. According to those data the ApK for methylamine (16) is proportional to the number of deuteriums, and for 16-18, 22, and 23 the Apper D or the AAG° per D is nearly constant, 24 cal mol-1. 

Abe, T. Pandey, S.K. Baba, H. Electrochemical fluorination of hexahydroazepine, methylpiperidines and methyl 1-hexahydroazepine-acetate the preparation of F-(l-hexahydroazepine-acetyl fluoride) and its derivatives. J. Fluorine Chem. 2000, 105 (1), 149-157. 

A soln. of bispiperidinomethylene and 1 mole phenyl isocyanide in toluene stirred and refluxed 10 hrs. amidine deriv. Y 41%. - Similarly with N-ethoxy-methylpiperidine -> ethyl N-phenylpiperidinoacetimidate. Y 38%. - Amidines and iminoesters not otherwise obtainable can be prepared by this reaction. F. e. s. O. Matsuda, K. Ito, and M. Sekiya, Chem. Pharm. Bull. 23, 219 (1975). 

Sahki, D. Belaiibi, B. F. Ait-Kaci, A. Jose, J. Static measurements of the total vapor pressure of hinaiy mixtures of morpholine -1- heptane and of piperidine or N-methylpiperidine -1- heptane or -1- decane between 273 K and 353 K ELDATA Int. 

A mixture of butyryl chloride and ethyl diazoacetate allowed to stand 10 days at room temp, in the presence of a few boiling stones ethyl butyryldiazo-acetate (Y 80%) dissolved with triphenylphosphine in abs. ether, which is then distilled off, the residue warmed 24 hrs. at 65° crude ethyl butyrylglyoxylate-2-triphenylphosphazine (Y 86%) dissolved in tetrahydrofuran free of 0x0 compounds, a little acetic acid added, then water added in 3 portions during 1 hr., allowed to stand 24 hrs. at room temp., the resulting crude hydrazone treated with N-methylpiperidine, a few boiling stones added, and warmed ca. 18 hrs. at 60° under anhydrous conditions until Ng-evolution ceases ethyl butyrylacetate (Y 77%).—Quinoline in abs. ethanol or pyridine may be used in place of N-methylpiperidine. F. e. s. H. J.Bestmann and H.Kolm, B. 96, 1948 (1963). 

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