Nitrogen methoxy methyl

Direct observation of singlet (alkyl)carbenes usually requires matrix isolation conditions. " Using the 7i-donor and a-attractor methoxy substituent, Moss and co-workers could characterize the (methoxy)(methyl)carbene (MeOCMe) by ultraviolet (UV) and infrared (IR) spectroscopies, but only in a nitrogen matrix (at 10 K) or in solution thanks to a nanosecond time-resolved LFP technique (fi/2 < 2ps at 20 °C). The remarkable stability of carbene XlVa both in the solid state and in solution (no degradation observed after several weeks at room temperature), prompted us to investigate the preparation of (phosphino)(alkyl)carbenes. 

Protection of the secondary alcohol as the corresponding methoxy methyl (MOM) ether, followed by removal of the Boc group with ZnBr2 in dichloromethane and acylation of the incipient secondary amine with bromoacetyl bromide in the presence of K2CO3 afforded the bromoacetamide 114 in 86% yield from 113. Treatment of 114 with methanolic ammonia afforded the corresponding glycinamide which was directly subjected to cyclization in the presence of NaH in toluene/HMPA to afford the bicyclic compound 115 in 79% overall yield from 114. Next, a one-pot double carbomethoxylation reaction was performed by the sequencial addition of n-BuLi in THF followed by addition of methylchloroformate, that carbomethoxylated the amide nitrogen atom. Subsequent addition of four equiv of methyl chloroformate followed by the addition of 5 equiv of LiN(TMS)2 afforded 116 as a mixture of diastereomers in 93% yield that were taken on directly without separation. 

The alkaloid lunarine, C26H33O6N3 (m.p. 224-226°), was obtained from this plant. Analysis of the chloroaurate indicated the presence of two basic nitrogens. Methoxy, methylenedioxy, and W-methyl groups are absent (120). Subsequently the formula of lunarine was altered to C26H31O4N3 (Hd 4-300°) and an additional alkaloid was described, namely lunaridine, C26H31O4N3 (m.p. 248-50°, +212). The absence of... 

Methoxy-cis-19-norpregna-l,3,5(10),17(20)-tetraene A solution of 31 g (109 mmolesi of estrone methyl ether in 600 ml of benzene is added rapidly to a solution of 469 mmoles of ethylidenetriphenylphosphorane in 1.2 liters of DMSO. After heating under nitrogen at 60° overnight, the reaction is cooled, poured into ice water, and extracted with three portions of hexane, backwashed with three portions of water and the hexane removed. The crude product, dissolved in petroleum ether (bp, 30-60°), is filtered through 225 g of alumina (activity I). The residue from the eluate consists of 95 % cis- and 5 % tran5-isomers, as determined by vpc analysis. After recrystallization from ether-methanol, 26.3 g (82%) of cw-isomer is obtained mp 76.5-77.5° [a]o 60°. 

When methyl 2-(indol-2-yl)acrylate derivative (22a) reacted with A-methoxy-carbonyl-l,2-dihydropyridine (8a) in refluxing toluene, in addition to the dimer of 22a (25%), a mixture of the expected isoquinculidine 23a and the product 24a (two isomers) was obtained in 7% and 45% yields, respectively (81CC37). The formation of 24a indicates the involvement of the 3,4-double bond of dihydropyridine. Similarly, Diels-Alder reaction of methyl l-methyl-2-(indol-2-yl)acrylate (22b) with 8a gave, in addition to dimer of 22b, a mixture of adducts 23b and 24b. However, in this case, product 23b was obtained as a major product in a 3 2 mixture of two isomers (with a- and (3-COOMe). The major isomer shows an a-conhguration. The yields of the dimer, 23b, and 24b were 25%, 30%, and 6%, respectively. Thus, a substituent on the nitrogen atom or at the 3-position of indole favors the formation of the isoquinuclidine adduct 23. 

Orthoesterification A mixture of 1 g of 6a a-difiuoroprednisolone, 10 mg of p-toluene-suifonic acid, 5 cc of dimethylformamide and 3 cc of methyl orthobutyrate is heated for 15 hours on an oil bath at 105°C while a slow stream of nitrogen is passed through the mixture so that the methanoi produced as a by-product of the reaction, is distilled off. After addition of severai drops of pyridine to neutralize the acid catalyst, the reaction mixture is evaporated under vacuum and there is obtained a solid residue which is taken up with methanol, and filtered. The product is recrystailized from a methylene chloride-methanol mixture to yieid 682 mg of 6a,9af[Pg.491]

D) 1-p-Chlorobenzoyl-2-Methyl-S-Methoxy-3-lndolylacetic Acid A mixture of 1 g ester and 0.1 g powdered porous plate is heated in an oil bath at 210°C with magnetic stirring under a blanket of nitrogen for about 2 hours. No intensification of color (pale yellow) occurs during this period. After cooling under nitrogen, the product is dissolved in benzene and ether, filtered, and extracted with bicarbonate. The aqueous solution is filtered with suction to remove ether, neutralized with acetic acid, and then acidified weakly with dilute hydrochloric acid. The crude product (0.4 g, 47%) is recrystallized from aqueous ethanol and dried in vacuo at 65°C MP 151°C. 

Likewise, thermolysis of 4-azidophenyl methyl ketone in methanol yields 5-acetyl-2-methoxy-3//-azepine (60%), compared to only an 8% yield from the photolytic reaction.78 119 The thermolysis of phenyl azide in refluxing cyclohexanol yields no 3H-azepine, only diphenyl-diazene (10%) and aniline (30%).74 In contrast, thermolysis of methyl 2-azidobenzoate in cyclohexanol furnishes a mixture of methyl 2-(cyclohexyloxy)-3//-azepine-3-carboxylate (20 % bp 127°C/0.1 Torr) and methyl 2-aminobenzoate (60%). Thermolysis of the azido ester in methanol under nitrogen in an autoclave at 150 C yields a 7 10 mixture (by 1HNMR spectroscopy) of the amino ester and methyl 2-methoxy-3//-azepine-3-carboxylate, which proved to be difficult to separate, and much tar.74 The acidic medium179 is probably responsible for the failure of methyl 2-azidoberjzoate to yield a 3//-azepine when thermolyzed in 3-methoxyphenol aniline (40%) is the major product.74... 

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