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 → HCID 86612090, compound

HRID 1674551Notes

Reaction equation

HRID 1674551 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:38][N:39](C1CC1)[CH2:40][CH2:41][CH2:42][CH:43]=[CH2:44])[C:10]([N:12]1[CH2:16][C@H:15]([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:14][C@H:13]1[C:25]([NH:27][C@:28]1([C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH2:30][C@H:29]1C=C)=[O:26])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:10](=[O:11])[N:12]2[C@@H:13]([CH2:14][C@@H:15]([O:17][Si:18]([C:21]([CH3:23])([CH3:22])[CH3:24])([CH3:19])[CH3:20])[CH2:16]2)[C:25](=[O:26])[NH:27][C@@:28]2([C:33]([O:35][CH2:36][CH3:37])=[O:34])[C@@H:30]([CH2:29]2)[CH:44]=[CH:43][CH2:42][CH2:41][CH2:40][NH:39][CH2:38]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

4

Reactant 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)-vinylcyclopropanecarboxylate

Product 1

HCID 86612090HCID 86612090, compoundYield 64.5%

Reagents, catalysts & solvents 2

HCID 11147261(1,3-Dimesitylimidazolidin-2-ylidene)(tricyclohexylphosphine)benzylidene ruthenium dichlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 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 (1.45 g, 2.14 mmol.) in 1 L of methylene chloride was added 181 mg (0.21 mmol.) of Grubb's 2nd generation catalyst [(1,3-Bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium]. The mixture was heated at reflux for 1 h. A second fraction of the catalyst (50 mg, 0.058 mmol) was added, and the mixture was stirred at rt overnight. The residue was concentrated in vacuo, and then purified by flash chromatography eluting with 50% ether/hexane to give 0.84 g (62%) of (1S,4R,6S,14S,18R)-7-cis-14-tert-Butoxycarbonylamino-18-(tert-butyldimethylsilyloxy)-2,15-dioxo-3,12,16-triazatricyclo[14.3.0.04,6]nonadec-7-ene-4-carboxylic acid, ethyl ester as a white solid: 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: 2.43 min), MS m/z 649 (M++1).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1 h
  3. concentrationThe residue was concentrated in vacuo
  4. custompurified by flash chromatography
  5. washeluting with 50% ether/hexane

Sources & evidence

ORD record
ord-41cc6dea2fca45f8bd682a3fb4bd2003
Source dataset
uspto-grants-2011_08
Patent number
US08003604B2

Reaction notes

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