Ammonium Chloride → N-Benzyl-(R)-alpha-methylbenzyl-3(S)-(6-methoxypyridin-3-yl)-beta-alanine ethyl ester

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Reaction Conditions

Reaction Steps

To a solution of N-benzyl-(R)-α-methylbenzylamine (97.5 g, 462 mmol) in THF (750 mL) at 0° C. was added n-butyllithium (2.5M in hexanes; 178.5 mL, 446 mmol). The dark violet solution was stirred at 0° C. for 20 minutes, cooled to -78° C. and the ester 7-3 (63.7 g, 308 mmol) in THF (250 mL) was added over 60 minutes. The resulting solution was stirred at -78° C. for 1 hr., then cannulated into saturated NH4Cl and extracted with EtOAc, washed with water then brine, dried and concentrated in vacuo to give an oil. Column chromatography (silica gel; hexane/EtOAc 9:1 then 4:1) gave 7-4 as an oil contaminated with N-benzyl-(R)-α-methylbenzylamine. This oil was taken up in 5% AcOH in water and extracted with diethyl ether (4×). The organic layers were dried over MgSO4 and the solvent removed to give the title compound 7-4. 1H NMR (300 MHz, CDCl3) δ 1.08 (3H, t), 1.27 (3H, d), 2.52 (1H, dd), 2.62 (1H, dd), 3.66 (1H, d), 3.70 (1H, d), 3.93 (3H, s), 3.95 (2H, m), 4.41 (1H, dd), 6.74 (1H, d), 7.15-7.45 (10H, m), 7.64 (1H, dd), 8.15 (1H, d).

Provenance & Evidence