Lithium Chloride → (2R,3R)-2-((tert-butyloxycarbonyl)amino)-3-((4-methylbenzyl)thio)-3-phenylpropionic acid

Participants

Reaction Conditions

Reaction Steps

The methyl ester 18 (380 mg, 0.91 mmol) and anhydrous lithium chloride (376 mg, 8.89 mmol) were dissolved in dry DMF (10 mL). The reaction mixture was heated at 90° C. for 4 days. The reaction mixture was cooled to room temperature, quenched with diluted HCl and extracted several times with ethyl acetate. The organic layer was washed with brine and dried over Na2SO4. The crude product was purified by flash column chromatography (silica, step gradient: 20% ethyl acetate/hexane, 25% ethyl acetate/5% acetic acid/hexane) to produce recovered starting material 18 (75 mg, 20%), followed by the desired carboxylic acid as a white solid, which was recrystallized (341 mg, 77%). mp 107°-108° C. (ether-hexane); [α]20D =-143.7° (c=1.66, CHCl3); 1H NMR (CDCl3).δ1.379 (s, 9H), 2.300 (s, 3H), 3.460 (d, J=13.3 Hz, 1H), 3.588 (d, J=13.3 Hz, 1H), 4.242 (d,J=5.5 Hz, H-3), 4.646 (dd, J=8.7, 5.5 Hz, 1H, H-2), 5.273 (bd, J=8.7 Hz, 1H, H--N), 7.055 (s, 4H), 7.259-7.340 (m, 5H); 13C NMR (CDCl3).δ21.1, 28.2, 35.5, 50.8, 58.1, 80.5, 127.9, 128.6, 128.9, 129.2, 133.9, 136.9, 138.1, 155.3, 174.5; MS m/z 401 ([M+H]+ ; Anal. Calcd. for C22H27O4NS: C, 65.81; H, 6.78; N, 3.48. Found: C, 65.83; H, 6.92; N, 3.57.

Provenance & Evidence