Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Thomas M. Koenig is active.

Publication


Featured researches published by Thomas M. Koenig.


Tetrahedron Letters | 1994

A convenient method for preparing enantiomerically pure norfluoxetine, fluoxetine and tomoxetine

Thomas M. Koenig; David Mitchell

Abstract A convenient synthesis for enantiomers of norfluoxetine, fluoxetine and tomoxetine is described. All final products were derived from a common intermediate, 3-phenyl-3-hydroxypropylamine.


Synthetic Communications | 1995

Synthesis of R- and S- Fluoxetine, Norfluoxetine and Related Compounds from Styrene Oxide

David Mitchell; Thomas M. Koenig

Abstract A facile, high yield synthesis of R—or S—fluoxetine and norfluoxetine is described. This synthetic route utilizes readily available starting materials.


Tetrahedron Letters | 1992

Regiospecific opening of 1,2-expoxides with acetone cyanohydrin under mildly basic conditions

David Mitchell; Thomas M. Koenig

Acetone cyanohydrin with stoichiometic triethylamine opens epoxides regiospecifically to give β-hydroxy nitriles. As expected, addition of cyanide occurs at the least substituted carbon.


Science | 2017

Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions.

Kevin P. Cole; Jennifer McClary Groh; Martin D. Johnson; Christopher L. Burcham; Bradley M. Campbell; William D. Diseroad; Michael R. Heller; John R. Howell; Neil J. Kallman; Thomas M. Koenig; Scott A. May; Richard D. Miller; David Mitchell; David P. Myers; Steven Scott Myers; Joseph L. Phillips; Christopher S. Polster; Timothy D. White; Jim Cashman; Declan Hurley; Robert Moylan; Paul Sheehan; Richard D. Spencer; Kenneth Desmond; Paul Desmond; Olivia Gowran

Continuous-flow technology is devised and implemented for manufacture of a drug candidate in clinical trials. Go with the flow in drug manufacturing Although many commodity chemicals are manufactured using continuous flow techniques, pharmaceuticals are still mostly produced in large single batches. Cole et al. report a protocol for the small-volume continuous preparation of multi-kilogram quantities of a cancer drug candidate, prexasertib monolactate monohydrate, under current good manufacturing practices. Advantages of the approach include safer handling of hazardous reagents and intermediates, as well as yield and selectivity improvements in both the reaction and purification stages. Concurrent analytical monitoring also facilitated rapid trouble-shooting during the manufacturing process. Science, this issue p. 1144 Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods. Success was enabled by advances in chemistry, engineering, analytical science, process modeling, and equipment design. Substantial technical and business drivers were identified, which merited the continuous process. The continuous process afforded improved performance and safety relative to batch processes and also improved containment of a highly potent compound.


Tetrahedron Letters | 1995

Ortho-hydroxyl assisted deoxygenation of phenones. Regiochemical control in the synthesis of monoprotected resorcinols and related polyphenolic hydroxyl systems

David Mitchell; Christopher W. Doecke; Lynne A. Hay; Thomas M. Koenig; David D. Wirth

A method for the selective protection of polyphenolic hydroxyls is described. This approach relies on the deoxygenation of a benzylic ketone ortho to at least one of the phenolic hydroxyl groups.


Tetrahedron Letters | 2003

Vinyl aryl ethers from copper-catalyzed coupling of vinyl halides and phenols

Zhonghui Wan; Chauncey D. Jones; Thomas M. Koenig; Y.John Pu; David Mitchell


Journal of Organic Chemistry | 1998

PALLADIUM-CATALYZED HYDROARYLATION OF PROPIOLAMIDES. A REGIO-AND STEREOCONTROLLED METHOD FOR PREPARING 3,3-DIARYLACRYLAMIDES

Lynne A. Hay; Thomas M. Koenig; Francis O. Ginah; James Densmore Copp; David Mitchell


Organic Process Research & Development | 2000

Identification and Comparison of Impurities in Fluoxetine Hydrochloride Synthesized by Seven Different Routes

David D. Wirth; Marybeth S. Miller; and Sathish K. Boini; Thomas M. Koenig


Organic Syntheses | 1998

SYNTHESIS OF UNSYMMETRICAL BIARYLS USING A MODIFIED SUZUKI CROSS-COUPLING : 4-BIPHENYLCARBOXALDEHYDE : (1,1-BIPHENYL-4-CARBOXALDEHYDE)

Bret E. Huff; Thomas M. Koenig; David Mitchell; Michael A. Staszak


Organic Process Research & Development | 2014

Use of Modeling and Process Analytical Technologies in the Design of a Catalytic Amination Reaction: Understanding Oxygen Sensitivity at the Lab and Manufacturing Scales

Jeremy M. Merritt; Jonas Y. Buser; Alison N. Campbell; Jared W. Fennell; Neil J. Kallman; Thomas M. Koenig; Hossam Moursy; Mark A. Pietz; Norma Scully; Utpal K. Singh

Collaboration


Dive into the Thomas M. Koenig's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Researchain Logo
Decentralizing Knowledge