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Chemical Structure| 1975218-55-3 Chemical Structure| 1975218-55-3

Structure of 1975218-55-3

Chemical Structure| 1975218-55-3

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Flavio S.P. Cardoso ; Appasaheb L. Kadam ; Ryan C. Nelson ; John W. Tomlin ; Dipendra Dahal ; Christopher S. Kuehner , et al.

Abstract: A low-cost, protecting group-free route to 6-(2-fluoro-4-nitrophenyl)-2-oxa-6-azaspiro[3.3]heptane (1), the starting material for the in-development tuberculosis treatment TBI-223, is described. The key bond forming step in this route is the creation of the azetidine ring through a hydroxide-facilitated alkylation of 2-fluoro-4-nitroaniline (2) with 3,3-bis(bromomethyl)oxetane (BBMO, 3). After optimization, this ring formation reaction was demonstrated at 100 g scale with isolated yield of 87% and final product purity of >99%. The alkylating agent 3 was synthesized using an optimized procedure that starts from tribromoneopentyl alcohol (TBNPA, 4), a commercially available flame retardant. Treatment of 4 with sodium hydroxide under Schotten–Baumann conditions closed the oxetane ring, and after distillation, 3 was recovered in 72% yield and >95% purity. This new approach to compound 1 avoids the previous drawbacks associated with the synthesis of 2-oxa-6-azaspiro[3,3]heptane (5), the major cost driver used in previous routes to TBI-223. The optimization and multigram scale-up results for this new route are reported herein.

Keywords: tuberculosis ; TBI-223 ; azaspiro[3.3]heptane ; spiroamine

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Product Details of [ 1975218-55-3 ]

CAS No. :1975218-55-3
Formula : C11H11FN2O3
M.W : 238.22
SMILES Code : O=[N+](C1=CC=C(N(C2)CC32COC3)C(F)=C1)[O-]

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