Indoles 1-methyl-, reduction

Methyl- or 3-Methyl-l //-indole by Reduction of the Corresponding (Trifluoromethyl)indole Typical Pro-cedures 67-145... 

Indole, 3-hydroxymethyl-2-phenyl-stability, 4, 272 Indole, l-hydroxy-2-phenyl-synthesis, 4, 363 Indole, 2-iodo-synthesis, 4, 216 Indole, 3-iodo-reactions, 4, 307 synthesis, 4, 216 Indole, 2-iodo-l-methyl-reactions, 4, 307 Indole, 2-lithio-synthesis, 4, 308 Indole, 3-lithio-synthesis, 4, 308 Indole, 2-mercapto-tautomerism, 4, 38, 199 Indole, 3-mercapto-tautomerism, 4, 38, 199 Indole, 3-methoxy-synthesis, 4, 367 Indole, 5-methoxy-oxidatlon, 4, 248 Indole, 7-methoxy-2,3-dimethyl-acetylation, 4, 219 benzoylation, 4, 219 Indole, 5-methoxy-l-methyl-reduction, 4, 256 Indole, 5-methoxy-l-methyl-3-(2-dimethylaminoethyl)-reactions... 

One route to o-nitrobenzyl ketones is by acylation of carbon nucleophiles by o-nitrophenylacetyl chloride. This reaction has been applied to such nucleophiles as diethyl malonatc[l], methyl acetoacetate[2], Meldrum s acid[3] and enamines[4]. The procedure given below for ethyl indole-2-acetate is a good example of this methodology. Acylation of u-nitrobenzyl anions, as illustrated by the reaction with diethyl oxalate in the classic Reissert procedure for preparing indolc-2-carboxylate esters[5], is another route to o-nitrobenzyl ketones. The o-nitrophenyl enamines generated in the first step of the Leimgruber-Batcho synthesis (see Section 2.1) are also potential substrates for C-acylation[6,7], Deformylation and reduction leads to 2-sub-stituted indoles. 

Acylation of the Leimgruber Batcho enamines with phosgene followed by methanolysis and reductive cyclization generates methyl indole-3-carb-oxylates[8]... 

Indole, l-methyl-2-sulfonamido-tautomerism, 4, 200 Indole, l-methyl-3-sulfonamido-tautomerism, 4, 200 Indole, (methylthio)-synthesis, 4, 368 Indole, 3-(methylthio)-synthesis, 4, 338, 368 Indole, l-methyl-3-vinyl-oxidation, 4, 280 Indole, nitro-rearrangement, 4, 297 Indole, 3-nitro-nitration, 4, 211, 213 reduction, 4, 362 synthesis, 4, 210, 363 Indole, 5-nitro-synthesis, 4, 211, 363 Indole, nitroso-rearrangement, 4, 297 Indole, 1-nitroso-reduction, 4, 362 Indole, 3-nitroso-reduction, 4, 362 Indole, nitrovinyl-... 

Indole-7-carbaldehyde, 1-methyl-synthesis, 4, 83 Indole-3-carbaldehydes synthesis, 2, 251 Indole-2-carboxamide reduction, 4, 256 synthesis, 4, 360 Indole-3-carboxamide synthesis, 4, 347... 

An interesting addition of ethyl acrylate has been reported in the case of l-methyl-2-ethylidenepyrrolidine. An unsaturated amino ketone 144 is formed, which rearranges to 1,7-dimethyloctahydroindole (145) on reduction with formic acid, as established by dehydrogenation to 1,7-dimethyl-indole (Scheme 12) 217). 

Representative procedure for conjugate reduction-aldol 3-CC 2- Hydroxy-[l-[tolue sulfonyl)- H-indol-3-yl]-methyl -4,4-dimethylcyclohexanone [35]... 

An excellent method for producing methyl indole-4-carboxylate from commercially available 3-nitro-2-methylbenzoic acid involves reduction of an intermediate nitroenamine (57). 

Woodward s strychnine synthesis commences with a Fischer indole synthesis using phenylhydrazine (24) and acetoveratrone (25) as starting materials (see Scheme 2). In the presence of polyphosphor-ic acid, intermediates 24 and 25 combine to afford 2-veratrylindole (23) through the reaction processes illustrated in Scheme 2. With its a position suitably masked, 2-veratrylindole (23) reacts smoothly at the ft position with the Schiff base derived from the action of dimethylamine on formaldehyde to give intermediate 22 in 92% yield. TV-Methylation of the dimethylamino substituent in 22 with methyl iodide, followed by exposure of the resultant quaternary ammonium iodide to sodium cyanide in DMF, provides nitrile 26 in an overall yield of 97%. Condensation of 2-veratryl-tryptamine (20), the product of a lithium aluminum hydride reduction of nitrile 26, with ethyl glyoxylate (21) furnishes Schiff base 19 in a yield of 92%. 

Cryptopine-type indole alkaloid bumamicine (572) has been synthesized from geissoschizine methyl ether (31) (287). In the first step, geissoschizol (34) was prepared, and then cleavage of the C/D ring fusion was carried out by means of ethyl chloroformate. Finally, C-3 carbonyl and 7V-methyl groups were developed by simple oxidation, reduction, and repeated oxidation steps. 

Molindone Molindone, 3-ethyl-6,7-dihydro-2-methyl-5-(morpholinomethyl)indol-4(5F0-one (6.4.3), is synthesized by the nitrozation of diethylketone using nitric acid or methyl-nitrite into nitrozodiethylketone (6.4.1). Reduction of this product with zinc in acetic acid into 2-aminodiethylketone in the presence of cyclohexandion-1,3 gives 3-ethyl-2-methyl-4,5,6,7-tetrahydroindol-4-one (6.4.2). Aminomethylation of this product using morpholine and formaldehyde gives molindone (6.4.3) [51-52]. 

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