Phthalic Anhydride → (2S)3-Benzyloxycarbonylamino-2-phthalimidopropionic acid

Temperature

0 °C

A solution of (2S) 3-benzyloxycarbonylamino-2-tert-butoxycarbonylaminopropionic acid dicyclohexylamine salt (3 g, 5.8 mmol) in dichloromethane (200 ml) was washed four times with 1M HCl solution, dried (MgSO4) and concentrated. The resulting oil was dissolved in dry dichloromethane (35 ml), cooled to 0° C. and treated with trifluoroacetic acid (35 ml). This solution was stirred at 0° C. for 1.5 h then evaporated to dryness. Dichloromethane (50 ml) was added to the residue then removed under vacuum. This process repeated six times to afford a white solid. The white solid was suspended in toluene (50 ml), treated with powdered phthalic anhydride (940 mg, 6.35 mmol) and refluxed for 18 h. The resulting solution was concentrated to afford an oil which was purified by flash chromatography (2-10% methanol/dichloromethane) to afford 266, 2.01 g (94%) as a white powder: IR (KBr) 3600-2500br, 1776, 1714, 1530, 1469, 1455, 1392, 1263, 1131, 722; 1H NMR (CDCl3) δ 7.83 (2H, m), 7.72 (2H, m), 7.29 (5H, m), 5.41 (1H, m), 5.03 (2H, s), 3.90 (2H, m); MS (ES-), 367 (M-1).

1. dry with materialdried (MgSO4)
2. concentrationconcentrated
3. dissolutionThe resulting oil was dissolved in dry dichloromethane (35 ml)
4. additiontreated with trifluoroacetic acid (35 ml)
5. customthen evaporated to dryness
6. additionDichloromethane (50 ml) was added to the residue
7. customthen removed under vacuum
8. customto afford a white solid
9. temperaturerefluxed for 18 h
10. concentrationThe resulting solution was concentrated
11. customto afford an oil which
12. customwas purified by flash chromatography (2-10% methanol/dichloromethane)

ORD record

ord-228d9bcaaa9c4b1a8041298dde13074b

Source dataset

uspto-grants-1999_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06008217