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Updated: Dec 27, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Synthesis of (R)-3-(tert-Butoxycarbonylamino)-4-(2,4,5-trifluorophenyl)butanoic Acid, a Key Intermediate, and the
Kurella Sreenivasulu1, Pramod S Chaudhari1, Srinivas Achanta1
1Integrated Product Development, Innovation Plaza, Dr. Reddy's Laboratories Ltd, Bachupally, Qutubullapur, R.R. Dist., 500072, Telangana, India.
Abstract:
An alternate formal synthesis of Sitagliptin phosphate is disclosed from 2,4,5-trifluorobenzadehyde in 8 linear steps with an overall yield of 31%. The chiral β-amino acid moiety present in sitaglitpin is installed via an asymmetric hydrogenation followed by a stereoselective Hofmann rearrangement as the key steps. The key chiral intermediate Boc-amino acid 1 prepared by this novel route was further converted to Sitagliptin phosphate following the known literature protocol.
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