Selectfluor → (S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-4-fluoro-1-oxo-1,2-dihydroisoquinolin-3-yl)ethylcarbamate

HRID 1051791Notes

Reaction equation

HRID 1051791 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][C:8]([C@@H:13]([NH:15][C:16](=[O:32])[O:17][CH2:18][CH:19]1[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:25]3[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH3:14])=[CH:7]2.[B-](F)(F)(F)[F:34].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][C:8]([C@@H:13]([NH:15][C:16](=[O:32])[O:17][CH2:18][CH:19]1[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:25]3[C:20]1=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH3:14])=[C:7]2[F:34]

Participants

4

Reactant 2

HCID 2724933SelectfluorHCID 68746456HCID 68746456, compound

Product 1

HCID 68747591(S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-4-fluoro-1-oxo-1,2-dihydroisoquinolin-3-yl)ethylcarbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of (S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-1-oxo-1,2-dihydroisoquinolin-3-yl)ethylcarbamate 79 (2.75 g, 6.1 mmol, 1.0 eq) and selectfluor (2.16 g, 6.1 mmol, 1.0 eq) in anhydrous acetonitrile (100 mL) was stirred at reflux under argon for 12 h. The mixture was allowed to cool to RT and then concentrated in vacuo. The residue was dissolved in ethyl acetate (100 mL) and filtered through celite. The filtrate was washed with water, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (10-50% ethyl acetate-hexanes) to afford the product (S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-4-fluoro-1-oxo-1,2-dihydroisoquinolin-3-yl)ethylcarbamate 80.

Workup

  1. temperatureat reflux under argon for 12 h
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (100 mL)
  4. filtrationfiltered through celite
  5. washThe filtrate was washed with water
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated in vacuo
  9. customthe residue was purified by flash column chromatography on silica gel (10-50% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-37981f6042774f83a2b2b3654c5bbd5f
Source dataset
uspto-grants-2016_07
Patent number
US09388183B2

Reaction notes

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