Acetic Acid → 1-(chloromethyl)-7-nitro-1,2-dihydro-3H-benzo[e]indole

HRID 2238388Notes

Reaction equation

HRID 2238388 reaction equation
[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([N+:16]([O-:18])=[O:17])=[CH:15][C:9]=3[CH:8]=[CH:7][C:6]=2[N:5](C(=O)C(F)(F)F)[CH2:4]1.C([O-])([O-])=O.[Cs+].[Cs+].CC(O)=O>O1CCOCC1.O.CO>[Cl:1][CH2:2][CH:3]1[C:11]2[C:10]3[CH:12]=[CH:13][C:14]([N+:16]([O-:18])=[O:17])=[CH:15][C:9]=3[CH:8]=[CH:7][C:6]=2[NH:5][CH2:4]1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 10796Cesium carbonateHCID 445491461-(chloromethyl)-3-(trifluoroacetyl)-7-nitro-1,2-dihydro-3H-benzo[e]indole

Product 1

HCID 593032481-(chloromethyl)-7-nitro-1,2-dihydro-3H-benzo[e]indoleYield 96%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 131 (1.00 g, 2.79 mmol) in dioxane (30 mL) was treated with a solution of Cs2CO3 (3.26 g, 10 mmol) in water (3 mL) and MeOH (17 mL), and the mixture was stirred vigorously at room temperature for 15 min. The resulting solution was treated with AcOH (1.2 mL), then concentrated to a small volume under reduced pressure and partitioned between water and CH2Cl2. The organic phase was washed with water (×2), dried, and filtered through a column of silica gel. Evaporation and trituration with petroleum ether/iPr2O gave 1-(chloromethyl)-7-nitro-1,2-dihydro-3H-benzo[e]indole (134) (702 mg, 96%) as an orange-red solid: mp (CH2Cl2/petroleum ether) 121-122° C.; 1H NMR [(CD3)2SO] δ 8.76 (d, J=2.2 Hz, 1H), 8.05 (dd, J=9.3, 2.3 Hz, 1H), 7.97 (d, J=8.7 Hz, 1H), 7.76 (d, J=9.3 Hz, 1H), 7.09 (d, J=8.7 Hz, 1H), 6.79 (s, 1H), 4.17-4.04 (m, 1H), 3.95-3.78 (m, 2H, 3.76-3.63 (m, 2H). Anal. (C13H11ClN2O2) C, H, N.

Workup

  1. concentrationconcentrated to a small volume under reduced pressure
  2. custompartitioned between water and CH2Cl2
  3. washThe organic phase was washed with water (×2)
  4. customdried
  5. filtrationfiltered through a column of silica gel
  6. customEvaporation and trituration with petroleum ether/iPr2O

Sources & evidence

ORD record
ord-b7925e37fade4a01a2a391737bd14dba
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Reaction notes

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