Development of a Scalable Synthetic Route to (1R,5R)-2,2-Dimethoxybicyclo[3.1.0]hexan-3-one: An Important Intermediate in the Synthesis of Lenacapavir DOI Creative Commons

Aline Souza,

Sakkani Nagaraju,

Daryl Guthrie

et al.

Organic Process Research & Development, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

(1R,5R)-2,2-Dimethoxybicyclo[3.1.0]hexan-3-one is used in the asymmetric synthesis of lenacapavir. Herein, we report an enantioselective this important chiral intermediate from inexpensive commodity (R)-epichlorohydrin. This synthetic method comprises 6 steps, including a 4-step telescoped bicyclic ketone synthesis, I2-promoted hydroxylation, and Albright–Goldman oxidation. sequence affords (1R,5R)-2,2-dimethoxybicyclo[3.1.0]hexan-3-one overall 25% isolated yield as enantiomerically pure compound. The entire process has been successfully demonstrated on hundred-gram scale.

Language: Английский

Development of a Scalable Synthetic Route to (1R,5R)-2,2-Dimethoxybicyclo[3.1.0]hexan-3-one: An Important Intermediate in the Synthesis of Lenacapavir DOI Creative Commons

Aline Souza,

Sakkani Nagaraju,

Daryl Guthrie

et al.

Organic Process Research & Development, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

(1R,5R)-2,2-Dimethoxybicyclo[3.1.0]hexan-3-one is used in the asymmetric synthesis of lenacapavir. Herein, we report an enantioselective this important chiral intermediate from inexpensive commodity (R)-epichlorohydrin. This synthetic method comprises 6 steps, including a 4-step telescoped bicyclic ketone synthesis, I2-promoted hydroxylation, and Albright–Goldman oxidation. sequence affords (1R,5R)-2,2-dimethoxybicyclo[3.1.0]hexan-3-one overall 25% isolated yield as enantiomerically pure compound. The entire process has been successfully demonstrated on hundred-gram scale.

Language: Английский

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