Die Synthese der 4‐Amino‐cyclohexyl‐(1)‐methylketone

Ferber, Erwin; Brückner, Hans

doi:10.1002/cber.19390720514

Cited by 11 publications

(5 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A solution of trarzs-3 (20 g) in 500 ml of 20% aqueous sodium hydroxide was refluxed for 8 h. The aqueous solution was then placed in a continuous extractor and the mixture was extracted with chloroform for a further 8 h. Compound 5 was obtained in 80% yield after recrystallization from ethyl acetate and melted at 110-1 1 lo, the melting point given by Ferber and Bruckner (16).…”

Section: Reduction Of 4 ( a ) In 2-propar101mentioning

confidence: 99%

Synthesis of 7-azabicyclo[2.2.1]heptane, exo-2-chloro-7-azabicyclo[2.2.1]heptane, and derivatives

Fraser¹,

Swingle²

1970

Can. J. Chem.

View full text Add to dashboard Cite

A synthesis of 7-azabicyclo[2.2.1]heptane (1) in five steps and an overall yield of 18 % has beenachieved. An alternative five-step route which gives 1 in 36% yield but which requires large amounts of platinum oxide has also been developed. In comparison, the only previous synthesis of this con~pound gave less than a 1 % overall yield of an impure product. Several N-acyl derivatives and the N-n~troso derivative have been prepared, and the barriers to rotation about the N-CO bond of the acetyl derivative and the N-NO bond of the nitroso derivative have been determined. The barriers were found to be 1.2 and 6.5 kcal less, respectively, than in their unstrained analogs. exo-2-Chloro-7-azabicyclo[2.2.l]heptane has also been synthesized.Canadian Journal of Chemistry, 48,2065Chemistry, 48, (1970 Considerable interest has recently developed in the nitrogen analogs of bicyclo [2.2.1 Iheptane. Reports on the synthesis and reactions of compounds containing nitrogen in the 1-position (1,2) and in the 2-position (3,4) have appeared. The 7-azabicyclo[2.2.1]heptane system has perhaps received more attention. In particular, many highly substituted derivatives have been produced by the Diels-Alder reactions of N-alkyl and N-acyl pyrroles with dimethylacetylene dicarboxylate (5-12). In contrast the parent 7-azabicyclo [2.2.1 Iheptane (1) was reported as synthesized only in impure form and was characterized by conversion to a picrate and a 7,7-dimethiodide derivative (12). Its synthesis from hydroquinone involved seven steps and gave 1 in an overall yield of less than 1 %. We wish to report an improvement in the synthesis of 1, which allows its preparation in yields of up to 36 %. The proof of structure of 1 is supported by its conversion to five derivatives, two of which are the subject of a temperature-dependent nuclear magnetic resonance (n.m.r.) investigation. In addition the exo-2-chloro derivative of 1 was synthesized and preliminary studies of its reactivity are reported.

show abstract

Section: Reduction Of 4 ( a ) In 2-propar101mentioning

confidence: 99%

Synthesis of 7-azabicyclo[2.2.1]heptane, exo-2-chloro-7-azabicyclo[2.2.1]heptane, and derivatives

Fraser¹,

Swingle²

1970

Can. J. Chem.

View full text Add to dashboard Cite

show abstract

“…The process mass intensity (PMI) was also slightly improved from 28 to 23 . In addition, use of the cheaper and more readily accessible trans -amino alcohol 13 allowed us to bypass the use of periodic acid and toxic molybdenum hexacarbonyl …”

Section: Resultsmentioning

confidence: 99%

Palladium-Catalyzed C–O Cross-Coupling as a Replacement for a Mitsunobu Reaction in the Development of an Androgen Receptor Antagonist

Hager

Guimond

Grunenberg

et al. 2021

Org. Process Res. Dev.

View full text Add to dashboard Cite

A scalable and efficient synthesis of N-{trans-4-[(8-cyanoquinolin-4-yl)oxy]cyclohexyl}-3-fluorobenzamide (BAY 1161116), an androgen receptor antagonist, is reported. The original synthesis included a low-yielding Mitsunobu reaction and employed cis-aminocyclohexanol, which is accessible only via a troublesome synthesis, as a key building block. The novel synthetic pathway starts from readily available trans-aminocyclohexanol and features a palladium-catalyzed etherification reaction in place of the Mitsunobu reaction as the key step. This four-step synthesis can be performed reliably on a multikilogram scale, and purification of all intermediates as well as the final product can be achieved by simple extraction and crystallization procedures.

show abstract

“…3-Hydroxymethylquinoxaline-2-carboxaldehyde 1,4-Di-JVoxide Semicarbazone (11). A mixture of 7 (4.4 g, 0.02 mol), semicarbazide hydrochloride (2.2 g, 0.02 mol), NaHC03 (1.7 g, 0.02 mol), and methanol (200 ml) was heated at reflux for 3 hr and filtered hot.…”

Section: Methodsmentioning

confidence: 99%