L-Proline, 4-hydroxy-, phenylmethyl ester, (4R)- synthesis

Yield:68172-39-4 87%

Reaction Conditions:

with toluene-4-sulfonic acid in benzene at 125; for 20 h;Dean-Stark;

Steps:

(2S,4R)-4-trans-hydroxyproline benzylester (12a)

To a solution of trans-4-hydroxyproline11a (1.5149 g, 11.55 mmol) in benzene (13.5 mL) and benzyl alcohol (13.5mL) was added p-toluenesulfonic acid monohydrate (2.0058 g, 11.65 mmol). The mixture was refluxed at 125 C for 20 h and H₂O was removed using a Dean Stark trap. The reaction mixture was then cooled to room temperature and the product crystallized upon the addition of diethyl ether (150 mL) to give a white solid in 87.0% yield. ¹H NMR (300 MHz, CD₃OD) δ: 2.094-2.206 (m, 1 H), 2.362 (s, 3 H), 2.399-2.491 (m, 1 H), 3.224-3.537 (m, 2H), 4.424-4.620 (m, 2 H), 5.233-5.336 (q, 2H, J = 12.3, 7.5, 6.6 Hz),7.213-7.239 (d, J = 7.8 Hz, 2 H), 7.295-7.380 (m, 5 H), 7.689-7.712 (d, J= 6.9 Hz, 2 H).

References:

Ley, Corinne R.;Beattie, Nathan R.;Dannoon, Shorouk;Regan, Melanie;VanBrocklin, Henry;Berkman, Clifford E. [Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,# 12,art. no. 22630,p. 2536 - 2539] Location in patent:supporting information