DR ANTHONY MELVIN CRASTO,WorldDrugTracker, helping millions, A 90 % paralysed man in action for you, I am suffering from transverse mylitis and bound to a wheel chair, With death on the horizon, nothing will not stop me except God................DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 25Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK GENERICS at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution

Friday 30 September 2016

A simple scale-up strategy for organolithium chemistry in flow mode: From feasibility to kilogram quantities









Synthesis of 2-Trifluoromethyl-4-fluorophenylboronic acid (2a)
2a: 2-Trifluoromethyl-4-fluorophenylboronic acid After reaching steady-state, the outcoming stream was quenched for 25 min (765 mmol) on 797 mL citric acid (10% in water) at 0 °C. After full addition, the mixture was stirred for 30 min at 0 °C and then warmed up to r.t. and stirred for another hour. The phases were separated and the water phase was extracted twice with 1.8 L isopropyl acetate. The organic phases were combined, washed with 20% NaClsolution (1.8 L) and dried in vacuum to yield the final product. The product was obtained as a slightly yellow solid. 146.1 g (HPLC purity at 210 nm = 97.4%). Yield = 89%.

1H NMR (400 MHz, DMSO-d6): δ = 8.00 (dd, J = 8.3, 6.6 Hz, 1H, Ar-H), 7.52 (dd, J = 9.9, 2.5 Hz, 1H, Ar-H), 7.55−7.45 (m, 1H, Ar-H) ppm.

13C NMR (100 MHz, DMSO-d6): δ = 162.6 (d, J = 247.0 Hz, CF), 138.1 (d, J = 7.9 Hz), 134.8 (dq, J = 31.6, 7.7 Hz), 133.8, 124.5 (dq, J = 274.8, 3.00 Hz, CF3), 118.4 (d, J = 19.2 Hz), 113.3 (dq, J = 24.2, 6.1 Hz) ppm.

 19F NMR (376 MHz, DMSO-d6): δ = −57.8 (s, 3F, CF3), −111.2 (s, 1F, CF) ppm. 11B-NMR (128 MHz, DMSO-d6): δ = 13.8 ppm. Analytical data is identical with the literature.1 [1] A. Hafner, M. Meisenbach, J. Sedelmeier, Org. Lett. 2016, 18, 3630-3633.




A simple scale-up strategy for organolithium chemistry in flow mode: From feasibility to kilogram quantities Andreas Hafner, Paolo Filipponi, Lorenzo Piccioni, Mark Meisenbach, Berthold Schenkel, Francesco Venturoni and Joerg Sedelmeier* Novartis Pharma AG, Fabrikstrasse 14, 4002 Basel, Switzerland Joerg.Sedelmeier@novartis.com  

No comments:

Post a Comment