HCID 67971799, compound → HCID 67035111, compound

HRID 1771923Notes

Reaction equation

HRID 1771923 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([N:14]([CH2:30]C=C)[C:15](=[O:29])[C@H:16]([NH:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([Cl:28])[CH:22]=2)[CH2:17][CH:18]=[CH2:19])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(Cl)Cl.CCOC(C)=O>[Cl:28][C:23]1[CH:22]=[C:21]([NH:20][C@@H:16]2[CH2:17][CH:18]=[CH:19][CH2:30][N:14]([C@@H:10]3[CH2:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:9]3)[C:15]2=[O:29])[CH:26]=[C:25]([F:27])[CH:24]=1

Participants

4

Reactant 1

HCID 67971799HCID 67971799, compound

Product 1

HCID 67035111HCID 67035111, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (R)-3-{allyl-[(R)-2-(3-chloro-5-fluoro-phenylamino)-pent-4-enoyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester (0.65 g, 1.4 mmol) in DCM (50 mL) was degassed and purged with argon. To the solution was added Grubb's 2nd generation catalyst (0.12 g, 0.13 mmol) and the mixture was refluxed for 90 minutes. After the solution was cooled to rt, the solvent was removed under reduced pressure to afford a solid which was dissolved in EtOAc. The organic phase was washed with brine, a solution of NaHCO3, dried (MgSO4), filtered and concentrated in vacuo to afford a residue which was purified by silica gel chromatography (gradient hexanes:EtOAc 0-70%). LCMS, m/z 381.9 [M−tBu]+.

Workup

  1. custompurged with argon
  2. temperaturethe mixture was refluxed for 90 minutes
  3. customthe solvent was removed under reduced pressure
  4. customto afford a solid which
  5. washThe organic phase was washed with brine
  6. dry with materiala solution of NaHCO3, dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a residue which
  10. customwas purified by silica gel chromatography (gradient hexanes:EtOAc 0-70%)

Sources & evidence

ORD record
ord-6cde1b1b3e274d808c200bd4f8d51b33
Source dataset
uspto-grants-2016_02
Patent number
US09249146B2

Reaction notes

Loading…