Yield: 99.25%

Reaction Conditions:

with 10 wt% Pd(OH)2 on carbon;hydrogen in methanol at 16; under 2068.65 Torr; for 16 h;

Steps:

To a solution of compound 133g (6.0 g, 26.89 mmol, 1.00 eq)) in MeOH (80.00 ml.) was added Pd(OH)₂/C (500.00 mg, 50.00 mmol, 10% purity, 1.86 eq) under N2. The suspension was degassed under vacuum and purged with H2 several times. The mixture was stirred under H₂ (40 psi) at 16°C for 16 hours. TLC (Petroleum ether/Ethyl acetate= 10: 1) showed the starting material was consumed completely and a new spot (Rf=0.4) was detected. The reaction mixture was filtered and the filter was concentrated to give compound 133h (5.18 g, 26.69 mmol, 99.25% yield, 99.5% purity) as brown solid, which was used in next step directly. ¹HNMR: (CD₃OD , 400 MHz) 6.66 (d, J = 8.5 Hz, 1H), 6.62 - 6.59 (m, 1H), 6.40 (ddd, J = 0.8, 2.7, 8.6 Hz, 1H).

References:

JANSSEN VACCINES & PREVENTION B.V.;VAN DONGEN, Maria;JURASZEK, Jaroslaw;SCHEPENS, Wim, Bert, Griet;LAWSON, Edward, Charles;SHOOK, Brian, C;JONCKERS, Tim, Hugo, Maria;TAHRI, Abdellah;RABOISSON, Pierre, Jean-Marie, Bernard;BUYCK, Christophe, Francis, Robert, Nestor WO2018/141854, 2018, A1 Location in patent:Page/Page column 32; 34