Reaktion #1884960

Reaktionsgleichung

Boc-L-4-hydroxyproline

N-methyl morpholine

HATU

ethyl 1(R)-amino-2(S)-vinylcyclopropanecarboxylate hydrochloride

→

ethyl 1(R)-[1-tert-butoxycarbonyl-4(R)-hydroxypyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate

Ausbeute 94.0%

Lösungsmittel

methylene chloride

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenconcentrated in vacuo
2. 2
   Sonstigeto give a brown oil
3. 3
   SonstigeThis was partitioned between ethyl acetate and sat. aq. NaHCO3
4. 4
   WaschenThe organic phase was washed with brine
5. 5
   Trocknendried (MgSO4)
6. 6
   Einengenconcentrated in vacuo

Vorschrift

A stirred slurry of Boc-L-4-hydroxyproline (N-Boc (2S,4R)-hydroxyproline) (10 g, 43.3 mmol) in 400 mL of methylene chloride was treated sequentially with N-methyl morpholine (9.3 mL, 84.7 mmol), HATU (19.5 g, 51.3 mmol), and ethyl 1(R)-amino-2(S)-vinylcyclopropanecarboxylate hydrochloride (9.1 g, 47.5 mmol). The gold homogeneous solution was stirred at rt under N2 for 18 h, and then concentrated in vacuo to give a brown oil. This was partitioned between ethyl acetate and sat. aq. NaHCO3. The organic phase was washed with brine, dried (MgSO4), and concentrated in vacuo to give 15 g (94%) of ethyl 1(R)-[1-tert-butoxycarbonyl-4(R)-hydroxypyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate as a off-white solid: LC-MS (Xterra HPLC column: 3.0×50 mm length. Gradient: 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B. Gradient time: 3 min. Hold time: 1 min. Flow rate: 5 mL/min. Detector Wavelength: 220 nm. Solvent A: 10% MeOH/90% H2O/0.1% TFA. Solvent B: 10% H2O/90% MeOH/0.1% TFA.) (Retention time: 2.09 min), MS m/z 369 (M++1).

Quelle