Tetrahydrofuran → HCID 60142090, compound

HRID 572483Notes

Reaction equation

HRID 572483 reaction equation
[CH3:1][C:2]([O:5][C@@H:6]([C:9]1[N:10]([CH3:28])[C:11](=[O:27])[C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[C:21]([CH3:26])[CH:20]=1)=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:7][OH:8])([CH3:4])[CH3:3].[O:29]1CCCC1.CC(=C(C)C)C.[O-]Cl=O.[Na+]>CS(C)=O.O>[C:2]([O:5][C@@H:6]([C:9]1[N:10]([CH3:28])[C:11](=[O:27])[C:12]2[C:17]([C:18]=1[C:19]1[CH:24]=[CH:23][C:22]([CH3:25])=[C:21]([CH3:26])[CH:20]=1)=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:7]([OH:29])=[O:8])([CH3:1])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 112502,3-Dimethyl-2-buteneHCID 23668197Sodium ChloriteHCID 68352804HCID 68352804, compound

Product 1

HCID 60142090HCID 60142090, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×

Procedure

A solution of 3-{(1S)-1-[(1,1-dimethylethyl)oxy]-2-hydroxyethyl}-4-(3,4-dimethylphenyl)-2-methyl-1(2H)-isoquinolinone (4 mg, 10.54 μmol) in DMSO is treated with DMP (13 mg, 0.032 mmol). After 18 h, the reaction mixture was filtered through a pad of silica gel and washed with 1:1 EtOAc-hexanes. The filtrate was concentrated, dissolved in EtOAc and washed with H2O (3×), brine, dried (Na2SO4), filtered and concentrated. The residue was then dissolved in tert-Butanol (51.5 μl) and Tetrahydrofuran (THF) (51 μl) and treated with 2,3-dimethyl-2-butene (3 μl, 0.02 mmol) and a solution of NaClO2 (1.787 mg, 0.016 mmol) and NaH2PO4 (1.2 mg, 10.5 μmol) in water (100 uL). The crude reaction mixture was diluted with water and extracted with EtOAc (3×). The combined organics were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was dissolved in DMF (250 uL) and purified by Gilson to afford the title compound: Rt=0.95, 0.97 (atropisomers), ES+ MS: 394 (M+1). The chirality of the above compound was established by comparison to authentic material of (R)- and (S)-(tert-butoxy)-2-(4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinolin-3-yl)acetic acid using a Chiral SFC 20% MeOH/80% CO2; 4.6×250 mm IC column; Rt (R)=1 min; (S)=7.22 min.

Workup

  1. filtrationthe reaction mixture was filtered through a pad of silica gel
  2. washwashed with 1:1 EtOAc-hexanes
  3. concentrationThe filtrate was concentrated
  4. dissolutiondissolved in EtOAc
  5. washwashed with H2O (3×), brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe residue was then dissolved in tert-Butanol (51.5 μl)
  10. customThe crude reaction mixture
  11. extractionextracted with EtOAc (3×)
  12. washThe combined organics were washed with brine
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated
  16. dissolutionThe residue was dissolved in DMF (250 uL)
  17. custompurified by Gilson

Sources & evidence

ORD record
ord-02eea76a7e9348e29ff87dac5a3fbc7f
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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