The Preparation of 1-Methyl-4-phenyl-4-cyanopiperidine

Novel cyclizations and ring-opening reactions of 3-phenylindene derivatives

“…The chloroform layer was separated, washed with water, and dried (anhydrous K2C03). The oil obtained by evaporation of the solvent was identified as Nmethyl-3-phenylspiro[indene-1,4'-piperidine] (2a): R¡ 0.4 on silica gel/MeOH-DMF (9:1); nmr (CDC13) S 7.2-7.8 (m, 9 H, aromatic), 6.90 (s, 1 H, =CH), 2.8-3.2 (m, 2 H, ring CH), 2.0-2.8 (m, 3 H, ring CH), 2.43 (s, 3 H, NCH3), 0.7-1.9 (m, 3 H, ring CH). 2a was converted to its hydrochloride salt (83%), mp 292-294°dec, which crystallized from isopropyl alcoholisopropyl ether.…”

“…Found: C, 86.33; H, 8.32; N, 4.74. 3-Phenylspiro |indan-1,4'-piperidine] Hydrochloride (3b).-A solution of the indene 2c (31.3 g, 0.12 mol) in 95% ethanol (100 ml) was hydrogenated in a Parr apparatus at 60 psi over a 10% palladium-on-carbon catalyst for 30 hr. After removal of the catalyst and solvent, the solid residue was dissolved in ether and extracted with 3 A HC1 (100 ml). The white precipitate that formed in the aqueous layer was collected and crystallized from 95% ethanol to yield 32 g (81%) of the indan 3b HC1: mp 238-Ánal.…”

“…A.•-A solution of 5 hydrochloride 3.15 g, 0.02 mol) in ethanol was hydrogenated in a Parr apparatus at 50 psi over a 10% palladium-on-carbon catalyst. After removal of the catalyst and solvent, the residue crystallized from acetone-isopropyl ether to yield 2.6 g (84%) of 8-ethyl-1,2,3,3a,8,8a-hexahydro-l-methyl-3a-phenylindeno [2,[1][2][3][4][5] pyrrole hydrochloride (8 HC1): mp 154-160°; nmr (CDCls) 3.0 (d, 7 = 4 Hz) and 2.6 (d, / = 4 Hz) due to A-methyl protons indicates a 50:50 mixture of isomers. 8 (free base): bp 143-146°( 0.1 mm); nmr (CCh) 7.0-7.4 (m, 9 H, aromatic), 2.4-3.2 (m, 6 H, >CH, NCH<, NCH2), 2.35 (s, 3 H, NCHs), 0.7-1.7 (m, 5 H, CH2CH3).…”

“…The dried (MgS04) solution was concentrated to a pale yellow oil (7.5 g), identified as 3-( 1-chloroethyl)-1-(2-ethoxycarbonylmethylamino)-1-phenylindene (10): R{ 0.4 by tic on silica gel/chloroform; ir absorption (film) at 1695 cm-1 [C(=0)]; nmr (CC14) 7.0-7.6 (m, 9 H, aromatic), 6.55 (s, 1 H, =CH), 5.15 (q, 1 H, tert-CH, J = 7 Hz), 4.1 (q, 2 H, OCH2, J = 7 Hz), 2.1-3.5 (m, 4 H, CH2), 2.75 (s, 3 H, NCH8), 1.95 (d, 3 H, =CCH3, J = 7 Hz), 1.2 (t, 3 H, CCHS, J = 7 Hz).…”

Synthesis of l-Carbethoxy-4-cyano-4-phenylpiperidine

“…Eisleb (I, 2) synthesized several piperidine compounds ; during the ring closure step of the synthesis, i.e., the reaction of benzyl cyanide with benzylbis(P-ch1oroethyl)amine in the presence of sodium amide and toluene, he obtained approximately 60% yield of product. Blicke et al (3) reported a 70% yield when a piperidine ring structure was formed through pyrolysis of a,a-di(&dimethyl-aminoethy1)-a-phenylacetonitrile. Kaiser and Hauser (4) indicated that the dialkylation of benzyl cyanide by alkyl halides in the presence of a strong base may take place uia the stepwise formation of carbanions or by the formation of a dianion.…”