Solifenacin N-Oxide synthesis

Yield:180272-28-0 83%

Reaction Conditions:

with sodium hydrogencarbonate;3-chloro-benzenecarboperoxoic acid in dichloromethane at 10 - 20; for 1 h;

Steps:

6 Example 6: Preparation of (rS,3/?)-3-[[(r-phenyl-r,2',3',4'-tetrahydro-2'-isoquinolyl)carbonyl] oxy] quinuclidine 1 -oxide (Impurity Z)
Dichloromethane (200 ml), sodium bicarbonate (5.16 g) and (lS,3 ^'i?)-quinuclidin-3 ^'-yl 1- phenyl-l,2,3,4-tetrahydro isoquinoline-2-carboxylate (19.0 g) were charged into a round bottom flask and cooled to 5°C, followed by the slow addition of m-chloroperbenzoic acid (14.10 g) at below 10°C and stirring for 60 minutes at ambient temperature. The reaction mass was quenched with water (250 ml).The organic layer was separated and washed with a solution of sodium thiosulphate (25.0 g) in water (250 ml) followed by fresh water (75 ml). The solvent was distilled off and degassed for 30 minutes under reduced pressure below 55°C to obtained crude (l£,3 'i?)-l '-oxido quinuclidin-3 '-yl 1 -phenyl- l ,2,3,4-tetrahydroisoquinoline-2-carboxylate (19.85 g). Purified by column chromatography using ethyl acetate and methanol to obtain pure (1 'S,3i?)-3 - [[( 1 '-phenyl- 1 ',2^*,3 ',4'-tetrahydro-2 ' -isoquinolyl)carbonyl]oxy] quinuclidine 1 -oxide (16.5 g). (Yield: 83%, Purity by HPLC 99.13%). NMR (CDCI3, δ ppm): 1.85-2.15 (m, 3H), 2.15-2.35 (m, 2H), 2.75-2.90 (m, 1H), 2.90-2.95 (m, 1 H), 3.20-3.50 (m, 6H), 3.70-3.80 (m, 1 H), 3.85-4.10 (m, 1H), 5.14 (brs, 1H), 6.14, 6.43 (brsx2, 1H), 7.05-7.40 (m, 9H). IR (cm^*1): 2966, 2937, 2879, 1695, 1689, 1425; MS: m/z: 379 (M+l).

References:

PHARMATHEN S.A.;KOFTIS, Theocharis, V.;SONI, Rohit, Ravikant;BODA, Bharat, Becharbhai;GHOTIKAR, Ravindra, Charudatta;PATEL, Vimal, Sudhirbhai WO2014/5601, 2014, A1 Location in patent:Page/Page column 10; 11

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