Réaction #1884989

ord-a99d6cb957ad4267b7111cc3de29a7e9

Équation de réaction

C=CCCCN(C[C@H](C(=O)OC(C)(C)C)C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@]1(C(=O)OCC)C[C@H]1C=C)C1CC1
compound 1c
C=CCCCN(C[C@H](C(=O)OC(C)(C)C)C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@]1(C(=O)OCC)C[C@H]1C=C)C1CC1
(1R,2S)-ethyl 1-((3R,5S)-1-((S)-2-(tert-butoxycarbonyl)-3-(cyclopropyl(pent-4-enyl)amino)propanoyl)-3-hydroxypyrrolidine-5-carboxamido)-2-vinylcyclopropanecarboxylate
c1c[nH]cn1
imidazole
CC(C)(C)[Si](C)(C)Cl
tert-butyldimethylsilyl chloride
→
C=CCCCN(C[C@H](C(=O)OC(C)(C)C)C(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]1C(=O)N[C@]1(C(=O)OCC)C[C@H]1C=C)C1CC1
(1R,2S)-ethyl 1-((3R,5S)-1-((S)-2-(tert-butoxycarbonyl)-3-(cyclopropyl(pent-4-enyl)amino)propanoyl)-3-(tert-butyldimethylsilyloxy)pyrrolidine-5-carboxamido)-2-vinylcyclopropanecarboxylate
Rendement 94.0%

Réactifs

C=CCCCN(C[C@H](C(=O)OC(C)(C)C)C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@]1(C(=O)OCC)C[C@H]1C=C)C1CC1
compound 1c
C=CCCCN(C[C@H](C(=O)OC(C)(C)C)C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@]1(C(=O)OCC)C[C@H]1C=C)C1CC1
(1R,2S)-ethyl 1-((3R,5S)-1-((S)-2-(tert-butoxycarbonyl)-3-(cyclopropyl(pent-4-enyl)amino)propanoyl)-3-hydroxypyrrolidine-5-carboxamido)-2-vinylcyclopropanecarboxylate
c1c[nH]cn1
imidazole
CC(C)(C)[Si](C)(C)Cl
tert-butyldimethylsilyl chloride

Réactifs

Aucun

Solvants

CN(C)C=O
DMF

Conditions de réaction

Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    Concentrationconcentrated in vacuo
  2. 2
    Autrepartitioned between ethyl acetate and water
  3. 3
    SéchageThe organic phase was dried over magnesium sulfate
  4. 4
    Concentrationconcentrated in vacuo
  5. 5
    Autreto obtain an off-white solid
  6. 6
    LavageFlash chromatography (eluting with methylene chloride

Mode opératoire

To a mixture of compound 1c (1.55 g, 2.75 mmoL) in 10 mL of DMF was added imidazole (0.47 g, 6.88 mmoL) and tert-butyldimethylsilyl chloride (826 mg, 5.50 mmoL). The mixture was stirred at rt for 18 h, concentrated in vacuo, and partitioned between ethyl acetate and water. The organic phase was dried over magnesium sulfate, and concentrated in vacuo to obtain an off-white solid. Flash chromatography (eluting with methylene chloride and then ethyl acetate) gave (1R,2S)-ethyl 1-((3R,5S)-1-((S)-2-(tert-butoxycarbonyl)-3-(cyclopropyl(pent-4-enyl)amino)propanoyl)-3-(tert-butyldimethylsilyloxy)pyrrolidine-5-carboxamido)-2-vinylcyclopropanecarboxylate 1d as a white solid (1.75 g, 94%): LC-MS (Phenomenex 10 μm C18 HPLC column: 3.0×50 mm length. Gradient: 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B. Gradient time: 2 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: 2.51 min), MS m/z 677 (M++1).

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US08343477B2uspto-grants-2013_01