(S)-4-tert-butyl 1-((R)-2-pent-4-enamido-2-phenylethyl) 2-allylsuccinate → tert-butyl 2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetate

HRID 41076Notes

Reaction equation

HRID 41076 reaction equation
[CH2:1]([C@@H:4]([CH2:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:5]([O:7][CH2:8][C@H:9]([NH:16][C:17](=[O:22])[CH2:18][CH2:19][CH:20]=C)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:6])[CH:2]=C>C1(C)C=CC=CC=1.Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1.C(Cl)Cl>[O:22]=[C:17]1[CH2:18][CH2:19][CH:20]=[CH:2][CH2:1][C@@H:4]([CH2:23][C:24]([O:26][C:27]([CH3:28])([CH3:29])[CH3:30])=[O:25])[C:5](=[O:6])[O:7][CH2:8][C@@H:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:16]1

Participants

5

Reactant 1

HCID 67310391(S)-4-tert-butyl 1-((R)-2-pent-4-enamido-2-phenylethyl) 2-allylsuccinate

Product 1

HCID 67311782tert-butyl 2-((3R,11S,E)-5,12-dioxo-3-phenyl-1-oxa-4-azacyclododec-8-en-11-yl)acetateYield 41%

Reagents, catalysts & solvents 3

HCID 178425456HCID 178425456, compoundCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of (S)-4-tert-butyl 1-((R)-2-pent-4-enamido-2-phenylethyl) 2-allylsuccinate (340 mg, 0.818 mmol) in toluene (82 mL) was added Grubbs 2nd Generation catalyst (34.7 mg, 0.041 mmol) and the reaction mixture was heated to 65° C. Upon stirring 7 h with continued heating, TLC analysis indicated complete consumption of starting material. The reaction mixture was cooled to rt, diluted with degassed CH2Cl2 (8.2 mL) and Pb(OAc)4 (181 mg, 0.409 mmol) was added. The resultant mixture was stirred for 12 h at which point the mixture was passed through a short plug of silica then concentrated using rotary evaporation. The resulting purple solid was triturated with methanol to further remove ruthenium complexes. The off white solid that remained was purified using silica gel chromatography (MeOH/CH2Cl2 gradient) to yield 130 mg of desired product as a white solid in 41% yield. LRMS (M+Na)+: 410.4.

Workup

  1. customconsumption of starting material
  2. temperatureThe reaction mixture was cooled to rt
  3. additionwas added
  4. concentrationthen concentrated
  5. customevaporation
  6. customThe resulting purple solid was triturated with methanol to further remove ruthenium complexes
  7. customThe off white solid that remained was purified

Sources & evidence

ORD record
ord-34ee3c46b5e64d67932e4f96abe3411e
Source dataset
uspto-grants-2013_09
Patent number
US08530456B2

Reaction notes

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