Fmoc-L-hydroxyproline synthesis

Yield:88050-17-3 150 g

Reaction Conditions:

with sodium hydrogencarbonate in tetrahydrofuran;water at 25 - 30;

Steps:

2 Synthesis of (2S, 4R)-1-[(9H-fluoren-9-ylmethoxy) carbonyl]-4-hydroxypyrrolidine-2-carboxylic acid
Example 2
Synthesis of (2S, 4R)-1-[(9H-fluoren-9-ylmethoxy) carbonyl]-4-hydroxypyrrolidine-2-carboxylic acid
To a solution of (2S,4R)-4-hydroxy-L-proline (100 g) in tetrahydrofuran (200 ml) was added sodium bicarbonate (80 g), water (400 ml) and 9-fluorenylmethyloxycarbonyl (Fmoc) chloride (226 g) solution (in 200 ml THF) at 25-30° C.
The reaction mixture was stirred at about 25-30° C. for about 10-12 h.
After completion of reaction, water was added.
Then the aq.
reaction mass was washed with diisopropyl ether (DIPE) and acidified with 1N hydrochloric acid.
The reaction mixture was stirred for about 2-3 hours.
The solid was collected by filtration to give the 150 g of title compound as white solid.
¹H NMR (300 MHz, DMSO-d6): δ 1.89-2.24 (m, 2H), 3.34-3.43 (m, 2H), 3:43-3.54 (m, 0.5H), 4.12-4.21 (m, 3H), 4.25 (s, 2H), 4.28-4.42 (m, 0.5H), 5.16 (brs, 1H), 7.29-7.34 (m, 2H), 7.38-7.65 (m, 21-1), 7.63-7.65 (m, 2H), 7.87-7.89 (m, 2H)
Melting point:-188-190° C.
Mass-(M+H):-354.33

References:

Glenmark Pharmaceuticals Limited;Kadam, Suresh Mahadev;Kansagra, Bipin Parsottam;Kale, Ramchandran Vishnue;Patil, Jayant Prakashrao;Yemireddy, Venkataramana Reddy;Bhadane, Shailendra Nilkanth;Chaudhar, Uddhav Popat;Patil, Ulhas Digambar;Bhirud, Shekhar Bhaskar US9518048, 2016, B2 Location in patent:Page/Page column 24

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