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

HRID 1668995Notes

Reaction equation

HRID 1668995 reaction equation
[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][CH2:10]2)=[CH:6][C:5]=1[NH2:13])([O-:3])=[O:2].[N+](C1C(N)=CC=C2C=1CCC2)([O-])=O.[CH3:27][C:28](OC(C)=O)=[O:29].NC1C=C2C(=CC=1)CCC2.[N+]([O-])([O-])=O.[K+]>O1CCOCC1.O>[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][CH2:10]2)=[CH:6][C:5]=1[NH:13][C:28](=[O:29])[CH3:27])([O-:3])=[O:2]

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 24434Potassium NitrateHCID 90496Indan-5-amineHCID 27636046-nitro-2,3-dihydro-1H-inden-5-amineHCID 128870504-Nitro-5-indanamine

Product 1

HCID 10751392N-(6-nitro-2,3-dihydro-1H-inden-5-yl)acetamideYield 24%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
20 °C

Procedure

6-Nitro-5-indanamine (2) and 4-Nitro-5-indanamine (3). Ac2O (15.6 mL, 165 mmol) was added dropwise to a stirred solution of 5-aminoindan (1) (10 g, 75.1 mmol) in dioxane (40 mL) at 5° C. and the solution stirred at 20° C. for 16 h. The solution was diluted with water (100 mL) and the precipitate filtered, washed with water (2×10 mL) and dried. The solid was dissolved in cH2SO4 (100 mL) and cooled to 5° C. A solution of KNO3 (8.35 g, 82.6 mmol) in cH2SO4 (15 mL) was added dropwise and the solution stirred at 5° C. for 2 h, then at 20° C. for 2 h. The solution was poured into ice/water (500 mL) and the suspension stirred for 2 h. The precipitate was filtered, washed with water (2×20 mL) and dried. The solid was purified by chromatography, eluting with a gradient (20-40%) of EtOAc/pet. ether, to give (i) N-(6-nitro-2,3-dihydro-1H-inden-5-yl)acetamide (3.97 g, 24%) as a colourless solid: mp (EtOAc/pet. ether) 105-108° C. [lit. (Schroeder, E., et al., European J. Med. Chem. 1982, 17, 35) mp 108-109° C.]; (ii) N-(4-nitro-2,3-dihydro-1H-inden-5-yl)acetamide (0.92 g, 5%) as a white solid: 1H NMR δ 9.51 (br s, 1H, NHCO), 8.28 (d, J=8.3 Hz, 1H, H-7), 7.41 (d, J=8.3 Hz, 1H, H-6), 3.25 (br t, J=7.5 Hz, 2H, H-1), 2.96 (br t, J=7.6 Hz, 2H, H-3), 2.22 (s, 3H, CH3), 2.07-2.13 (m, 2H, H-2); 13C NMR δ 164.1, 143.3, 142.1, 134.6, 131.9, 130.9, 117.3, 35.5, 32.1, 24.9; and (iii) N-(7-nitro-2,3-dihydro-1H-inden-5-yl)acetamide (6.48 g, 39%) as a white solid: 1H NMR δ 7.94 (s, 1H, H-5), 7.89 (s, 1H, H-7), 7.44 (br s, 1H, NHCO), 3.36 (br t, J=7.5 Hz, 2H, H-3), 2.92 (br t, J=7.6 Hz, 2H, H-1), 2.20 (s, 3H, CH3), 2.09-2.18 (m, 2H, H-2).

Workup

  1. filtrationthe precipitate filtered
  2. washwashed with water (2×10 mL)
  3. customdried
  4. dissolutionThe solid was dissolved in cH2SO4 (100 mL)
  5. temperaturecooled to 5° C
  6. stirringthe solution stirred at 5° C. for 2 h
  7. waitat 20° C. for 2 h
  8. stirringthe suspension stirred for 2 h
  9. filtrationThe precipitate was filtered
  10. washwashed with water (2×20 mL)
  11. customdried
  12. customThe solid was purified by chromatography
  13. washeluting with a gradient (20-40%) of EtOAc/pet. ether

Sources & evidence

ORD record
ord-86bea97b748344b798a53bbde7b4ece9
Source dataset
uspto-grants-2011_08
Patent number
US07989451B2

Reaction notes

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