反应详情

Intermediate 6 (50 mg, 0.15 mmol) was added to a colourless solution of L-phenylalanine cyclopentyl ester (89 mg, 0.38 mmol) in MeOH (10 ml) at RT/N2 and stirred at RT for 1 h. AcOH glacial was added dropwise to adjust the pH to 6 followed by the NaCNBH3 (38 mg, 0.61 mmol). The resultant colourless solution was stirred at RT overnight and then carefully quenched with sat. NaHCO3 (20 ml) and extracted into CH2Cl2 (3×15 ml). The combined organic phases were washed with 2M HCl (2×20 ml), brine (20 ml), dried (Na2SO4), filtered and concentrated in vacuo giving a cream coloured solid. Purification by flash column chromatography (silica, gradient elution 40-100% EtOAc/heptane) gave the desired material, separable as two isomers, isomer 1 (Example 34) as a white solid (Yield=39 mg, 47%) LCMS purity 100%, m/z 546 [M+H]+, 1H NMR (400 MHz, CD3OD), δ: 1.40-2.05 (16H, m), 2.85-3.10 (3H, m), 3.60-3.70 (1H, m), 4.55-4.65 (1H, m), 5.10-5.20 (1H, m), 5.70 (1H, d), 7.15-7.40 (7H, m), 7.45-7.50 (1H, m), 7.50-7.60 (2H, m) and isomer 2 (Example 35) LCMS purity 97%, m/z 546 [M+H]+, 1H NMR (400 MHz, CD3OD), δ: 1.25-1.85 (12H, m), 1.95-2.20 (2H, m), 2.45-2.95 (4H, m), 3.00-3.10 (1H, m), 3.65-3.75 (1H, m), 4.55-4.65 (1H, m), 5.05-5.15 (1H, m), 5.65 (1H, d), 7.20-7.35 (7H, m), 7.40-7.50 (1H, m), 7.50-7.60 (2H, m) as a colourless film (Yield=15 mg, 18%).

1. stirringThe resultant colourless solution was stirred at RT overnight
2. customcarefully quenched with sat. NaHCO3 (20 ml)
3. extractionextracted into CH2Cl2 (3×15 ml)
4. washThe combined organic phases were washed with 2M HCl (2×20 ml), brine (20 ml)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customgiving a cream
9. customPurification
10. washby flash column chromatography (silica, gradient elution 40-100% EtOAc/heptane)