Hydrogen Peroxide → N-(6-nitro-2,3-dihydro-1H-inden-5-yl)acetamide

HRID 1669030Notes

Reaction equation

HRID 1669030 reaction equation
OO.C(O[C:10]([C:12](F)(F)F)=[O:11])(C(F)(F)F)=O.COC1CCN(CCNC2N=[N+:29]([O-:40])[C:30]3[CH:39]=[C:38]4[C:34]([CH2:35][CH2:36][CH2:37]4)=[CH:33][C:31]=3[N:32]=2)CC1.C(O)(C(F)(F)F)=[O:42]>C(Cl)Cl.N>[N+:29]([C:30]1[CH:39]=[C:38]2[C:34]([CH2:35][CH2:36][CH2:37]2)=[CH:33][C:31]=1[NH:32][C:10](=[O:11])[CH3:12])([O-:40])=[O:42]

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 6422Trifluoroacetic acidHCID 9845Trifluoroacetic anhydrideHCID 11951117N-[2-(4-Methoxy-1-piperidinyl)ethyl]-7,8-dihydro-6H-indeno[5,6-e][1,2,4]triazin-3-amine 1-Oxide

Product 1

HCID 10751392N-(6-nitro-2,3-dihydro-1H-inden-5-yl)acetamide

Reagents, catalysts & solvents 2

HCID 222AmmoniaSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

H2O2 (70%, 3.1 mL, ca. 62.6 mmol) was added dropwise to a stirred solution of TFAA (8.8 mL, 62.6 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 42 (2.15 g, 6.3 mmol) and TFA (2.4 mL, 31.3 mmol) in DCM (50 mL) at 0° C. The solution was stirred at 20° C. for 8 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with DCM (4×50 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-15%) of MeOH/DCM, to give (i) starting material 42 (204 mg, 9%); and (ii) 1,4-dioxide 43 (1.0 g, 44%) as a red solid: mp (MeOH/EtOAc) 148-151° C.; 1H NMR δ 8.11 (s, 1H, H-9), 8.10 (s, 1H, H-5), 7.44 (br s, 1H, NH), 3.61-3.66 (m, 2H, CH2N), 3.33 (s, 3H, OCH3), 3.22-3.29 (m, 1H, CHO), 3.10 (br t, J=7.5 Hz, 2H, H-6), 3.05 (br t, J=7.5 Hz, 2H, H-8), 2.75-2.81 (m, 2H, CH2N), 2.68 (br t, J=6.0 Hz, 2H, CH2N), 2.27-2.34 (m, 2H, CH2N), 2.20 (p, J=7.5 Hz, 2H, H-7), 1.87-1.95 (m, 2H, CH2), 1.61-1.70 (m, 2H, CH2); 13C NMR δ 155.6, 149.4, 145.8, 138.0, 129.7, 115.7, 111.6, 75.8, 56.3, 55.5, 50.7 (2), 38.3, 33.4, 32.4, 30.6 (2), 25.6. Anal. calcd for C18H25N5O3.¼H2O: C, 59.4; H, 7.1; N, 19.2. Found: C, 59.2; H, 6.8; N, 19.1%.

Workup

  1. temperaturewarmed to 20° C. for 10 min
  2. temperaturecooled to 0° C.
  3. stirringThe solution was stirred at 20° C. for 8 h
  4. extractionextracted with DCM (4×50 mL)
  5. customThe combined organic fraction was dried
  6. customthe solvent evaporated
  7. customThe residue was purified by chromatography
  8. washeluting with a gradient (0-15%) of MeOH/DCM

Sources & evidence

ORD record
ord-44bc5815d11540a782f8b734528bce81
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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