38029-99-1Relevant articles and documents
Synthesis of Amides from Alcohols and Amines Through a Domino Oxidative Amidation and Telescoped Transamidation Process
Drageset, Audun,Bj?rsvik, Hans-René
, p. 4436 - 4445 (2018/09/11)
The amide bond formation is of paramount importance in organic synthesis, both within academic research and industrial development and manufacturing of pharmaceutical chemicals and other biologically active compounds. Despite this fact, as well as the ever-increasing treatment costs of side streams and other environmental concerns regarding handling and transportation of hazardous reagents, contemporary synthesis has elicited few new reactions and methods for the preparation of amides. Herein, we reveal a high yielding and expedite two-step telescoped synthetic process that comprises a domino oxidative amidation and transamidation for the creation of amides. The process utilizes alcohols and amines as reaction pairs with TEMPO and Fe ions as catalytic system and 1,3-dichloro-5,5-dimethyl hydantoin as a terminal oxidant. The oxidative amidation and transamidation process is conducted under benign reaction conditions and short reaction time (≈ 30 min.) in a two-step telescoped fashion by means of a multi-jet oscillating disk (MJOD) continuous-flow reactor platform. The disclosed process integrates alcohol oxidation and amide formation to afford target amide in yields up to 90 %. The method operates with both primary and secondary amines together, but was hampered when bulky amines and/or alcohols were used as reagent/substrate.
Practical racemic and asymmetric formal total syntheses of the homocamptothecin derivative and anticancer agent diflomotecan via tertiary homoallylic alcohols as masked aldol equivalents
Peters, Rene,Diolez, Christian,Rolland, Alain,Manginot, Eric,Veyrat, Marc
, p. 255 - 273 (2008/03/12)
An efficient and scalable racemic as well as an asymmetric approach to the key building block for the synthesis of homocamptothecin and derivatives thereof such as the potent anticancer agent diflomotecan (4) are described. In the asymmetric route, the pyridone ring was assembled applying straightforward carbonyl chemistry. The selective generation of the quaternary stereocenter was accomplished by self reproduction of chiral information starting from (S)-2-hydroxybutyric acid (22) utilizing an allyl moiety to act as a masked carbonyl group. The optically pure DE building block (7) (er > 99.95 : 0.05) was obtained in 9.0% overall yield over 10 steps (two chromatographic purifications). The asymmetric "de novo pyridone approach" has the potential to serve as the basis for a technical synthesis of diflomotecan.
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Dormoy, Jean-Robert,Heymes, Alain
, p. 2885 - 2914 (2007/10/02)
Total synthesis of modified ellipticines 1c and 1f is described from 2-chloronicotinic acid and respectively 5-methoxy -indole and 5-azaindole in 11 to 13 steps with overall yields of 11% and 18%. A new route to 5-azaindole has also been developed. The synthetic strategy calls for frequent use of homo- and hetero aromatic metallation reactions necessiting resolution of problems associated with the presence of the pyridine ring. With respect to the numerous synthesis described in the litterature, the originality of this approach resides above all in the formation of ring C in basic medium.1 such conditions being dictated by the presence of the pyridine A ring in the case of 1f. Both synthesis have been extrapolated to produce several kilogrammes of final product. That first part deals with the preparation of the precursors.