Dichloromethane → tert-butyl 1-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-carbamate

HRID 2238443Notes

Reaction equation

HRID 2238443 reaction equation
[N+:1]([C:4]1[C:5]2[CH:22]=[C:21](C(O)=O)[CH:20]=[CH:19][C:6]=2[C:7]2[CH2:8][CH2:9][N:10]([C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[C:11]=2[CH:12]=1)([O-:3])=[O:2].[C:26](Cl)(=[O:30])C(Cl)=O.[N-:32]=[N+]=[N-].[Na+].[CH3:36][C:37]([OH:40])([CH3:39])[CH3:38].[CH2:41]([Cl:43])Cl>CN(C=O)C.O>[Cl:43][CH2:41][CH:8]1[C:7]2[C:6]3[CH:19]=[CH:20][C:21]([NH:32][C:26]([O:40][C:37]([CH3:39])([CH3:38])[CH3:36])=[O:30])=[CH:22][C:5]=3[C:4]([N+:1]([O-:3])=[O:2])=[CH:12][C:11]=2[N:10]([C:13](=[O:18])[C:14]([F:17])([F:15])[F:16])[CH2:9]1

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 6386tert-ButanolHCID 33557Sodium AzideHCID 65578Oxalyl chlorideHCID 866202665-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-carboxylic acid

Product 1

HCID 86620265tert-butyl 1-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-carbamateYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 962WaterSolvent

Procedure

A suspension of 220 (410 mg, 1.02 mmol) in CH2Cl2 (15 mL) containing DMF (1 drop) was treated with oxalyl chloride (0.27 mL, 3.10 mmol) and stirred at room temperature for 30 min. The mixture was evaporated under reduced pressure and azeotroped dry with benzene. The resulting acid chloride was dissolved in acetone (5 mL) and treated at 0° C. with a solution of NaN3 (300 mg, 4.6 mmol) in water (1 mL). The mixture was shaken at room temperature for 1 min, and the precipitate was collected, dried, and stirred in toluene (15 mL) at reflux for 1.5 h. After addition of t-BuOH (1.0 mL, 10 mmol) the mixture was heated at reflux for 5 min then concentrated under reduced pressure. The residue was purified by chromatography, eluting with CH2Cl2, followed by crystallisation from CH2Cl2/hexane to give tert-butyl 1-(chloromethyl)-5-nitro-3-(trifluoroacetyl)-1,2-dihydro-3H-benzo[e]indole-7-carbamate (221) (347 mg, 72%) as an orange solid: mp 219-220° C.; 1H NMR [(CD3)2SO] δ 9.93 (s, 1H), 8.94 (s, 1H), 8.71 (d, J=1.9 Hz, 1H), 8.19 (d, J=9.2 Hz, 1H), 7.82 (dd, J=9.2, 2.0 Hz, 1H), 4.65-4.42 (m, 3H), 4.17 (dd, J=11.3, 2.8 Hz, 1H), 4.09 (dd, J=11.3, 5.2 Hz, 1H), 1.52 (s, 9H). Anal. (C20H19ClF3N3O5) C, H, N.

Workup

  1. customThe mixture was evaporated under reduced pressure
  2. customazeotroped
  3. dry with materialdry with benzene
  4. dissolutionThe resulting acid chloride was dissolved in acetone (5 mL)
  5. stirringThe mixture was shaken at room temperature for 1 min
  6. customthe precipitate was collected
  7. customdried
  8. stirringstirred in toluene (15 mL)
  9. temperatureat reflux for 1.5 h
  10. temperaturewas heated
  11. temperatureat reflux for 5 min
  12. concentrationthen concentrated under reduced pressure
  13. customThe residue was purified by chromatography
  14. washeluting with CH2Cl2
  15. customfollowed by crystallisation from CH2Cl2/hexane

Sources & evidence

ORD record
ord-98f2e359f9f74c738592793c29e09fb6
Source dataset
uspto-grants-2010_05
Patent number
US07718688B2

Reaction notes

Loading…