Dimethylformamide → (S)-(9H-fluoren-9-yl)methyl 1-(1,8-dichloroisoquinolin-3-yl)ethylcarbamate

HRID 518264Notes

Reaction equation

HRID 518264 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=O)[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.CN(C=O)C.S(Cl)([Cl:40])=O>C1(C)C=CC=CC=1>[Cl:40][C:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[Cl:1])[CH:7]=[C:8]([C@@H:13]([NH:15][C:16](=[O:32])[O:17][CH2:18][CH:19]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:25]3[C:20]2=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH3:14])[N:9]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 68746456HCID 68746456, compound

Product 1

HCID 86665027(S)-(9H-fluoren-9-yl)methyl 1-(1,8-dichloroisoquinolin-3-yl)ethylcarbamate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of (S)-(9H-fluoren-9-yl)methyl 1-(8-chloro-1-oxo-1,2-dihydroisoquinolin-3-yl)ethylcarbamate (345) (58 g, 130 mmol, 1.0 eq) and DMF (0.5 mL) in toluene (300 mL), sulfurous dichloride (78 g, 0.65 mol, 5.0 eq) was added slowly, and the resulting mixture was stirred at reflux for 2.5 h. The mixture was allowed to cool to RT and then concentrated in vacuo. The residue was poured into water (200 mL) and extracted with ethyl acetate (3×100 mL). The organic layer was washed with water (2×100 mL) and brine (100 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (5-20% ethyl acetate-petroleum ether) to afford (S)-(9H-fluoren-9-yl)methyl 1-(1,8-dichloroisoquinolin-3-yl)ethylcarbamate (346).

Workup

  1. temperatureat reflux for 2.5 h
  2. concentrationconcentrated in vacuo
  3. additionThe residue was poured into water (200 mL)
  4. extractionextracted with ethyl acetate (3×100 mL)
  5. washThe organic layer was washed with water (2×100 mL) and brine (100 mL)
  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 (5-20% ethyl acetate-petroleum ether)

Sources & evidence

ORD record
ord-ee679c1f4af946a889f40eed7f3443d5
Source dataset
uspto-grants-2015_08
Patent number
US09115141B2

Reaction notes

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