1-Fluoro-4-prop-2-ynyl-benzene → Tert-butyl 5-(6-(5-(4-fluorobenzyl)isoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate

HRID 927279Notes

Reaction equation

HRID 927279 reaction equation
Cl[O-].[Na+].[F:4][C:5]1[CH:10]=[CH:9][C:8]([N:11]2[C:20]([CH2:21][CH2:22][CH2:23][CH2:24][C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[CH:19][C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH:32]=[N:33][OH:34])[CH:17]=3)[C:12]2=[O:35])=[CH:7][CH:6]=1.[F:36][C:37]1[CH:42]=[CH:41][C:40]([CH2:43][C:44]#[CH:45])=[CH:39][CH:38]=1>ClCCl>[F:36][C:37]1[CH:42]=[CH:41][C:40]([CH2:43][C:44]2[O:34][N:33]=[C:32]([C:16]3[CH:17]=[C:18]4[C:13](=[CH:14][CH:15]=3)[C:12](=[O:35])[N:11]([C:8]3[CH:9]=[CH:10][C:5]([F:4])=[CH:6][CH:7]=3)[C:20]([CH2:21][CH2:22][CH2:23][CH2:24][C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])=[CH:19]4)[CH:45]=2)=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 105586681-Fluoro-4-prop-2-ynyl-benzeneHCID 23665760Sodium HypochloriteHCID 118558147Tert-butyl 5-(2-(4-fluorophenyl)-6-((hydroxyimino)methyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate

Product 1

HCID 90094533Tert-butyl 5-(6-(5-(4-fluorobenzyl)isoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoateYield 78.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Sodium hypochlorite (1.408 mL, 0.912 mmol) was added to a stirred, room temperature mixture of tert-butyl 5-(2-(4-fluorophenyl)-6-((hydroxyimino)methyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (100 mg, 0.228 mmol) and 1-fluoro-4-(prop-2-ynyl)benzene (61.2 mg, 0.456 mmol) in dichloromethane (2 mL), and the mixture was stirred at room temperature for overnight. The reaction was checked with LCMS and starting material was all consumed. The mixture was diluted with dichloromethane (10 mL), washed with aqueous sodium hydrogen carbonate (saturated, 1×8 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with EtOAc/isohexane=50% to give tert-butyl 5-(6-(5-(4-fluorobenzyl)isoxazol-3-yl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (102 mg, 0.179 mmol) as a yellow solid.

Workup

  1. washwashed with aqueous sodium hydrogen carbonate (saturated, 1×8 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel
  6. washeluting with EtOAc/isohexane=50%

Sources & evidence

ORD record
ord-e5bce5144a7c4478adb8c6139f23d3ee
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

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