Methanesulfonyl chloride → 3-(tert-butyloxycarbonyl)-1-chloromethyl-5-nitro-1,2-dihydro-3H-benz[e]indole

HRID 366804Notes

Reaction equation

HRID 366804 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14]([N+:17]([O-:19])=[O:18])[C:13]3[CH:20]=[CH:21][CH:22]=[CH:23][C:12]=3[C:11]=2[CH:10]([CH2:24]O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S([Cl:30])(C)(=O)=O.S([O-])(=O)(=O)C.[Li+].[Cl-]>N1C=CC=CC=1.O.CN(C=O)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH:15]=[C:14]([N+:17]([O-:19])=[O:18])[C:13]3[CH:20]=[CH:21][CH:22]=[CH:23][C:12]=3[C:11]=2[CH:10]([CH2:24][Cl:30])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 31297Methanesulfonyl chlorideHCID 85257MethanesulfonateHCID 433294Lithium ChlorideHCID 107124643-(tert-butyloxycarbonyl)-1-hydroxymethyl-5-nitro,1,2-dihydro-3H-benz[e]indole

Product 1

HCID 153804133-(tert-butyloxycarbonyl)-1-chloromethyl-5-nitro-1,2-dihydro-3H-benz[e]indoleYield 77%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 1049PyridineSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

A stirred solution of 12 (0.42 g, 1.22 mmol) in pyridine (1.8 mL) was treated dropwise at 0° C. with mesyl chloride (1.13 mL, 1.46 mmol) and then stirred at 20° C. for a further 2 h. The mixture was diluted with water and the resulting solid was collected, dissolved in CH2Cl2, and the solution was washed twice with water, dried (Na2SO4) and evaporated under reduced pressure below 30° C. A mixture of the resulting crude mesylate and LiCl (0.21 g, 5 mmol) in DMF (4 mL) was stirred at 80° C. for 30 min, then cooled and diluted with water. The precipitated solid was dissolved in CH2Cl2 and filtered through a column of silica gel to give a crude product which was triturated with iPr2O/petroleum ether, yielding 3-(tert-butyloxycarbonyl)-1-chloromethyl-5-nitro-1,2-dihydro-3H-benz[e]indole (13) (0.34 g, 77%). A sample recrystallised from iPr2 o/petroleum ether had mp 168-169° C. 1H NMR (CDCl3) δ8.88 (br s, 1 H, H-9), 8.42 (br s, 1 H, H-7), 7.80 (d, J=8.1 Hz, 1 H, H-4), 7.67-7.51 (m, 2 H, H-5,6), 4.34 (br s, 1 H, H-2), 4.20 (t, J=10.2 Hz, 1 H, H-2), 4.17-4.08 (m, 1 H, H-3), 3.92 (dd, J=11.2, 2.5 Hz, 1 H, CHHCl), 3.54 (t, J=10.3 Hz, CHHCl), 1.62 (s, 9 H, C(CH3)3).

Workup

  1. customthe resulting solid was collected
  2. dissolutiondissolved in CH2Cl2
  3. washthe solution was washed twice with water
  4. dry with materialdried (Na2SO4)
  5. customevaporated under reduced pressure below 30° C
  6. stirringwas stirred at 80° C. for 30 min
  7. temperaturecooled
  8. filtrationfiltered through a column of silica gel
  9. customto give a crude product which
  10. customwas triturated with iPr2O/petroleum ether

Sources & evidence

ORD record
ord-69555dce7a7144239adb6449ae8606cb
Source dataset
uspto-grants-2000_10
Patent number
US06130237

Reaction notes

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