4-Methylmorpholine → Ethyl (3R)-3-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate

To a stirred solution of N-BOC-D-phenylglycine (5.02 g, 20 mmol), N-methylmorpholine (2.02 g, 20 mmol) in EtOAc (100 mL) at 0° C. was added isobutyl chloroformate (2.73 g, 20 mmol). After 15 minutes the reaction mixture was filtered to remove the amine salts then an ethereal solution of diazomethane (60 mL, 30 mmol) was added. The cooling bath was removed and the reaction mixture stirred at ambient temperature for 2 hours. The reaction mixture was purged with nitrogen for 15 minutes to remove the excess diazomethane. The reaction mixture was diluted with EtOAc, washed with 1N HCl , saturated NaHCO3, and dried (MgSO4). Evaporation of the solvent afforded the crude diazoketone which was dissolved in EtOH (100 mL) and then treated sequentially with AgO2CPh (1.6 g, 7 mmol) and triethylamine (6.06 g, 60 mmol). After 20 hours the reaction mixture was concentrated and chromatographed (silica gel, 15% EtOAc/hexanes) affording 4.90 g (85%) of product as a colorless oil. 1H-NMR (300 MHz, CDCl3) δ1.17 (t, J=7 Hz, 3H), 1.43 (s, 9H), 2.73-2.92 (m, 2H), 4.07 (q, J=7 Hz, 2H), 5.10 (m, 1H), 5.48 (m, 1H), 7.22-7.39 (m, 5H).

1. filtrationAfter 15 minutes the reaction mixture was filtered
2. customto remove the amine salts
3. customThe cooling bath was removed
4. customThe reaction mixture was purged with nitrogen for 15 minutes
5. customto remove the excess diazomethane
6. additionThe reaction mixture was diluted with EtOAc
7. washwashed with 1N HCl , saturated NaHCO3
8. dry with materialdried (MgSO4)
9. customEvaporation of the solvent
10. customafforded the crude diazoketone which
11. concentrationAfter 20 hours the reaction mixture was concentrated
12. customchromatographed (silica gel, 15% EtOAc/hexanes)

ORD record

ord-17d5dfeccdea47ea8e1da7a9a927cc5b

Source dataset

uspto-grants-1996_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05484946