Acetic Acid → Tert-butyl 1-{2-[4-(methoxycarbonyl)phenyl]ethyl}-5-oxo-d-prolinate

To a solution of H-D-Glu(OtBu)-OtBu (0.5 g, 2.23 mmol) in MeOH (15 mL) were added 4-carbomethoxyphenylacetaldehyde (obtained from methyl 4-formyl benzoate as described in J. Med. Chem. 1989, 32, 1277-1283) (0.4 g, 2.23 mmol), acetic acid (0.15 mL, 2.67 mmol), and NaCNBH3 (3.3 mL, 1.0 M THF solution, 3.3 mmol). The resulting solution was stirred at RT for 3 h then was diluted with EtOAc (100 mL) and washed with water (50 mL), and brine (50 mL). The organic solution was dried over sodium sulfate and concentrated in vacuo. The crude oil was diluted with xylene and the solution refluxed for 5 h. This solution was concentrated under reduced pressure and purified by silica gel column chromatography using EtOAc/hexane as eluent to afford the title compound (0.75 g, 75%) as a white solid. Rf0.45 (EtOAc/hexane 1/1); 1H NMR (CDCl3) δ 1.47 (s, 9H), 1.95-2.05 (m, 1H), 2.10-2.20 (m, 1H), 2.25-2.35 (m, 1H), 2.40-2.50 (m, 1H), 2.80-3.00 (m, 2H), 3.10-3.20 (m, 1H), 3.82 (dd, 1H), 3.91 (s, 3H), 3.90-4.01 (m, 1H), 7.25 (d, 2H), 7.96 (d, 2H).

1. washwashed with water (50 mL), and brine (50 mL)
2. dry with materialThe organic solution was dried over sodium sulfate
3. concentrationconcentrated in vacuo
4. additionThe crude oil was diluted with xylene
5. temperaturethe solution refluxed for 5 h
6. concentrationThis solution was concentrated under reduced pressure
7. custompurified by silica gel column chromatography

ORD record

ord-54cc5ee19bfc4621a47dbe9c3f198106

Source dataset

uspto-grants-2008_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07419999B2