HCID 59269826, compound → HCID 59269825, compound

HRID 1666972Notes

Reaction equation

HRID 1666972 reaction equation
[CH2:1]([S:4][C@:5]1([C:32]2[CH:37]=[CH:36][C:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH:34][CH:33]=2)[CH2:9][N:8]([C:10](=[O:27])[C@@H:11]([NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH:17]=C)[C@H:7]([C:28]([O:30][CH3:31])=[O:29])[CH2:6]1)[CH:2]=C.SC1N=CC=CC=1C(O)=O>ClCCl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[C:35]1([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:36]=[CH:37][C:32]([C@@:5]23[CH2:9][N:8]([C@H:7]([C:28]([O:30][CH3:31])=[O:29])[CH2:6]2)[C:10](=[O:27])[C@@H:11]([NH:19][C:20]([O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:21])[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH:17]=[CH:2][CH2:1][S:4]3)=[CH:33][CH:34]=1

Participants

5

Reactant 2

HCID 59269826HCID 59269826, compoundHCID 178524460HCID 178524460, compound

Product 1

HCID 59269825HCID 59269825, compoundYield 71.4%

Reagents, catalysts & solvents 2

HCID 11763533(1,3-Bis(2,4,6-trimethylphenyl)imidazolidin-2-ylidene)(dichloro)((2-((propan-2-yl)oxy)phenyl)methylidene)rutheniumCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of (2S,4R)-methyl 4-(allylthio)-4-(biphenyl-4-yl)-1-((S)-2-(tert-butoxycarbonylamino)non-8-enoyl)pyrrolidine-2-carboxylate (123 mg, 0.203 mmol) in Dichloromethane (50 mL) was purged with nitrogen for 30 min. And then Hoveyda-Grubbs Catalyst 2nd Generation (153 mg, 0.243 mmol) was added. The resulting green solution was heated to reflux for 5 h. The reaction was quenched with 2-Mercaptonicotinic acid (62.9 mg, 0.405 mmol) and washed with sat. Na2CO3, and brine. Dried over MgSO4, filtered, concentrated in vacuo. The brown residue was purified by Biotage column, eluted with gradient 5%˜40% EtOAc-Hexane to afford the desired product (3S,13R,15S,E)-methyl 13-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-ene-15-carboxylate (93 mg, 0.145 mmol, 71.3% yield) as an off-white solid. NMR analysis showed the configuration of the double bond is exclusively trans. 1H NMR (500 MHz, MeOD) δ ppm 1.39-1.55 (m, 13 H), 1.55-1.75 (m, 4 H), 1.81-1.92 (m, 1 H), 1.97-2.08 (m, 1 H), 2.20-2.31 (m, 1 H), 2.57 (dd, J=12.82, 7.93 Hz, 1 H), 2.76-2.85 (m, 1 H), 2.92 (dd, J=15.87, 7.93 Hz, 1 H, 3.68-3.80 (m, 3 H), 4.20 (t, J=7.78 Hz, 1 H), 4.31-4.40 (m, 1 H), 4.52-4.65 (m, 2 H), 5.65 (dd, J=14.19, 6.87 Hz, 1 H), 5.85 (dd, J=14.95, 7.32 Hz, 1 H), 7.36 (t, J=7.32 Hz, 1 H), 7.41-7.50 (m, 2 H), 7.58-7.74 (m, 6 H). LC-MS (retention time: 3.42 min, method C), MS m/z 579 (M+H).

Workup

  1. temperatureThe resulting green solution was heated
  2. temperatureto reflux for 5 h
  3. washwashed with sat. Na2CO3, and brine
  4. dry with materialDried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe brown residue was purified by Biotage column
  8. washeluted with gradient 5%˜40% EtOAc-Hexane

Sources & evidence

ORD record
ord-c5d9db81d3ea40e5970f6d3bb4437e6f
Source dataset
uspto-grants-2011_10
Patent number
US08044087B2

Reaction notes

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