Imidazole → ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-(tert-butyldimethylsilyloxy)pyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate

HRID 2358353Notes

Reaction equation

HRID 2358353 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:31][N:32]([CH:38]1[CH2:40][CH2:39]1)[CH2:33][CH2:34][CH2:35][CH:36]=[CH2:37])[C:10]([N:12]1[CH2:16][C@H:15]([OH:17])[CH2:14][C@H:13]1[C:18]([NH:20][C@:21]1([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:23][C@H:22]1[CH:24]=[CH2:25])=[O:19])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CN=C1.[Si:46](Cl)([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47]>CN(C=O)C>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:31][N:32]([CH:38]1[CH2:40][CH2:39]1)[CH2:33][CH2:34][CH2:35][CH:36]=[CH2:37])[C:10]([N:12]1[CH2:16][C@H:15]([O:17][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[CH2:14][C@H:13]1[C:18]([NH:20][C@:21]1([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:23][C@H:22]1[CH:24]=[CH2:25])=[O:19])=[O:11])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 59386563ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-hydroxypyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate

Product 1

HCID 67331048ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-(tert-butyldimethylsilyloxy)pyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylateYield 94%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-hydroxypyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate (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 ethyl 1(R)-[1-[2(S)-(tert-butoxycarbonylamino)-3-[N-cyclopropyl-N-(pent-4-enyl)amino]propanoyl]-4(R)-(tert-butyldimethylsilyloxy)pyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate as a white solid (1.75 g, 94%):

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-e4ac6345443b4a599b900bb8c7e4f5bc
Source dataset
uspto-grants-2010_07
Patent number
US07763584B2

Reaction notes

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