Cesium carbonate → [7-Fluoro-2-(4-nitro-phenyl)-1-oxo-1,2-dihydro-isoquinolin-6-yl]-carbamic acid tert-butyl ester

HRID 1593044Notes

Reaction equation

HRID 1593044 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][N:8]([C:13]3[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=3)[C:9]2=[O:12])=[CH:4][C:3]=1OS(C(F)(F)F)(=O)=O.[C:30](=[O:37])([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[NH2:31].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1COCC1>[C:33]([O:32][C:30](=[O:37])[NH:31][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[F:1])[C:9](=[O:12])[N:8]([C:13]1[CH:14]=[CH:15][C:16]([N+:19]([O-:21])=[O:20])=[CH:17][CH:18]=1)[CH:7]=[CH:6]2)([CH3:36])([CH3:35])[CH3:34]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58998446Trifluoromethanesulfonic acid 7-fluoro-2-(4-nitro-phenyl)-1-oxo-1,2-dihydro-isoquinolin-6-yl ester

Product 1

HCID 58998509[7-Fluoro-2-(4-nitro-phenyl)-1-oxo-1,2-dihydro-isoquinolin-6-yl]-carbamic acid tert-butyl esterYield 80.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
75 °C

Procedure

In a dry flask was combined trifluoromethanesulfonic acid 7-fluoro-2-(4-nitro-phenyl)-1-oxo-1,2-dihydro-isoquinolin-6-yl ester (0.86 g, 2 mmol), t-butyl carbamate (0.33 g, 2.8 mmol), dry powdered cesium carbonate (1.1 g, 3.4 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos, 0.14 g, 0.24 mmol), and tris(dibenzylideneacetone)dipalladium(0) (Pd2dba3, 38 mg, 0.08 mmol). Under Ar atmosphere, dry THF (17 mL) was added to the flask, and the mixture was stirred at 75° C. for 25 hr. The reaction was concentrated and purified on silica gel using EtOAc/hexane as eluent to give 0.64 g (80%) of pure [7-Fluoro-2-(4-nitro-phenyl)-1-oxo-1,2-dihydro-isoquinolin-6-yl]-carbamic acid tert-butyl ester as a white solid. RP-HPLC: 5.98 min; ES-MS (M+H)+=400.0; 1H-NMR (DMSO-d6) δ (ppm): 1.47 (s, 9), 6.77 (d, 1), 7.46 (d, 1), 7.78 (d, 2), 7.87 (d, 1), 8.17 (d, 1), 8.33 (d, 2), 9.54 (s, 1).

Workup

  1. customIn a dry flask was combined
  2. concentrationThe reaction was concentrated
  3. custompurified on silica gel

Sources & evidence

ORD record
ord-17215c51b5e2405e93230ec8078ecb62
Source dataset
uspto-grants-2007_11
Patent number
US07294635B2

Reaction notes

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