Ammonia → 2-Trimethylsilanylethyl (s)-4-(-2-tert-butoxycarbonylamino-2-carboxypent-4-enyl)piperidine-1-carboxylate

110 ml of ammonia were condensed at −78° C. 1 g of sodium was added in 3 portions at intervals each of 10 min, and the mixture was stirred for 20 min. Then, at −60° C., a solution of 2.76 g of tert-butyl (3S,5S,6R)-3-allyl-2-oxo-5,6-diphenyl-3-[1-(2-trimethylsilanylethoxycarbonyl)piperidin-4-ylmethyl]morpholine-4-carboxylate and 2.6 ml of ethanol in 50 ml of THF was added dropwise. The mixture was stirred at −45° C. for 1.5 h and the reaction was stopped by adding solid ammonium chloride until the blue color disappeared. The ammonia was then allowed to evaporate off, and 300 ml of water were added to the residue. The THF was removed in vacuo. The aqueous was adjusted to pH 2 with 1 N HCl and extracted 3 times with 200 ml of ethyl acetate each time. The combined organic phases were dried with MgSO4. The solvents were removed in vacuo, and the residue was chromatographed on silica gel.

1. customcondensed at −78° C
2. stirringThe mixture was stirred at −45° C. for 1.5 h
3. customto evaporate off
4. addition300 ml of water were added to the residue
5. customThe THF was removed in vacuo
6. extractionextracted 3 times with 200 ml of ethyl acetate each time
7. dry with materialThe combined organic phases were dried with MgSO4
8. customThe solvents were removed in vacuo
9. customthe residue was chromatographed on silica gel

ORD record

ord-b8f54d931ff643ab8a6db62419cb861c

Source dataset

uspto-grants-2006_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07008957B2