Triethylamine → methyl 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valyl-(4R)-4-[(7-methoxy-3-vinylquinoxalin-2-yl)oxy]-L-prolinate

HRID 1008856Notes

Reaction equation

HRID 1008856 reaction equation
[CH3:1][C:2]([CH3:42])([CH3:41])[C@@H:3]([C:16]([N:18]1[CH2:26][C@H:25]([O:27][C:28]2[C:37](Cl)=[N:36][C:35]3[C:30](=[CH:31][C:32]([O:39][CH3:40])=[CH:33][CH:34]=3)[N:29]=2)[CH2:24][C@H:19]1[C:20]([O:22][CH3:23])=[O:21])=[O:17])[NH:4][C:5]([O:7][C@@H:8]1[CH2:10][C@H:9]1[CH2:11][CH2:12][CH2:13][CH:14]=[CH2:15])=[O:6].[B-](F)(F)(F)[CH:44]=[CH2:45].[K+].C(N(CC)CC)C>CCO.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH3:1][C:2]([CH3:42])([CH3:41])[C@@H:3]([C:16]([N:18]1[CH2:26][C@H:25]([O:27][C:28]2[C:37]([CH:44]=[CH2:45])=[N:36][C:35]3[C:30](=[CH:31][C:32]([O:39][CH3:40])=[CH:33][CH:34]=3)[N:29]=2)[CH2:24][C@H:19]1[C:20]([O:22][CH3:23])=[O:21])=[O:17])[NH:4][C:5]([O:7][C@@H:8]1[CH2:10][C@H:9]1[CH2:11][CH2:12][CH2:13][CH:14]=[CH2:15])=[O:6]

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 23679353Potassium vinyltrifluoroborateHCID 78358296(2S,4R)-methyl 4-((3-chloro-7-methoxyquinoxalin-2-yl)oxy)-1-((S)-3,3-dimethyl-2-((((1R,2R)-2-(pent-4-en-1-yl)cyclopropoxy)carbonyl)amino)butanoyl)pyrrolidine-2-carboxylate

Product 1

HCID 67304070methyl 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valyl-(4R)-4-[(7-methoxy-3-vinylquinoxalin-2-yl)oxy]-L-prolinate

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution (0.1 M) of methyl 3-methyl-N-({[(1R,2R)-2-pent-4-en-1-ylcyclopropyl]oxy}carbonyl)-L-valyl-(4R)-4-[(3-chloro-7-methoxyquinoxalin-2-yl)oxy]-L-prolinate in EtOH was treated with potassium trifluoro(vinyl)borate (1.5 eq) and triethylamine (1.5 eq). The resulting mixture was degassed, then PdCl2(dppf)-CH2Cl2 adduct (0.1 eq) was added. The mixture was heated under reflux for 1 h, then cooled to room temperature and diluted with H2O and EtOAc. The organic phase was separated, washed with H2O and brine then dried. Removal of the volatiles afforded a residue that was purified by flash chromatography (20-30% EtOAc/petroleum ether) to give the title compound as a yellow foam that was used directly in the subsequent step. MS (ES+) m/z 595 (M+H)+

Workup

  1. customThe resulting mixture was degassed
  2. temperatureThe mixture was heated
  3. temperatureunder reflux for 1 h
  4. customThe organic phase was separated
  5. washwashed with H2O and brine
  6. customthen dried
  7. customRemoval of the volatiles
  8. customafforded a residue that
  9. customwas purified by flash chromatography (20-30% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-c74d25d195274ef88bd9975ccfb2bfc2
Source dataset
uspto-grants-2011_07
Patent number
US07973040B2

Reaction notes

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