Imidazole → HCID 86619966, compound

HRID 1797807Notes

Reaction equation

HRID 1797807 reaction equation
[C:1]([O:5][C:6]([C@@H:8]([CH2:30][N:31]([CH:37]1[CH2:39][CH2:38]1)[CH2:32][CH2:33][CH2:34][CH:35]=[CH2:36])[C:9]([N:11]1[C@H:15]([C:16]([NH:18][C@:19]2([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:21][C@H:20]2[CH:22]=[CH2:23])=[O:17])[CH2:14][C@@H:13]([OH:29])[CH2:12]1)=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[Si:45](Cl)([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46]>CN(C=O)C>[C:1]([O:5][C:6]([C@@H:8]([CH2:30][N:31]([CH:37]1[CH2:39][CH2:38]1)[CH2:32][CH2:33][CH2:34][CH:35]=[CH2:36])[C:9]([N:11]1[C@H:15]([C:16]([NH:18][C@:19]2([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH2:21][C@H:20]2[CH:22]=[CH2:23])=[O:17])[CH2:14][C@@H:13]([O:29][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])[CH2:12]1)=[O:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86619965HCID 86619965, compound

Product 1

HCID 86619966HCID 86619966, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customto obtain an off-white solid
  6. washFlash chromatography (eluting with methylene chloride

Sources & evidence

ORD record
ord-a99d6cb957ad4267b7111cc3de29a7e9
Source dataset
uspto-grants-2013_01
Patent number
US08343477B2

Reaction notes

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