Isopropyl iodide → 1-Isopropyl-7-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one

HRID 1040998Notes

Reaction equation

HRID 1040998 reaction equation
[N+:1]([C:4]1[CH:15]=[CH:14][C:7]2[NH:8][C:9](=[O:13])[CH2:10][CH2:11][CH2:12][C:6]=2[CH:5]=1)([O-:3])=[O:2].[H-].[Na+].[H][H].[CH:20](I)([CH3:22])[CH3:21]>CN(C=O)C.O>[CH:20]([N:8]1[C:9](=[O:13])[CH2:10][CH2:11][CH2:12][C:6]2[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:15]=[CH:14][C:7]1=2)([CH3:22])[CH3:21]

Participants

7

Reactant 4

HCID 6362Isopropyl iodideHCID 24758Sodium hydrideHCID 3561757-nitro-2,3,4,5-tetrahydro-1H-1-benzazepin-2-oneHCID 178418361HCID 178418361, compound

Product 1

HCID 672639191-Isopropyl-7-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-oneYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

7-Nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (500 mg, 2.42 mmol) was dissolved in 10 ml anhydrous DMF and the reaction cooled to 0° C. Sodium hydride (140 mg, 3.6 mmol) was charged and the reaction allowed to stir at 0° C. until hydrogen evolution ceases. Isopropyl iodide (1.45 ml, 14.50 mmol) was charged and the reaction allowed to warm to room temperature over night. In the morning, a new peak matching the desired mass was determined by LC/MS. The reaction was poured into 50 ml water and extracted with 3×25 ml portions of methylene chloride. The combined organic was washed with 2×10 ml portions water and 10 ml brine, dried over magnesium sulfate, filtered and evaporated. The resulting crude product was purified via silica gel chromatography on a 40 g Isco cartridge using a gradient of 0-70% ethyl acetate in hexanes to yield 1-Isopropyl-7-nitro-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (474 mg, 79% yield) as a white solid. 1H-NMR (CDCl3) δ 8.16 (d, J=8.8 Hz, 1H), 8.11 (s, 1H), 7.34 (d, J=8.7 Hz, 1H), 4.78 (m, 1H), 2.78 (m, 1H), 2.78 (br s 2H), 2.32 (br s, 2H), 2.16 (br s, 1H), 1.98 (br s, 1H), 1.48 (br s, 2H), 1.14 (br s, 2H). LC/MS (ESI+)=249 (M+H).

Workup

  1. temperatureto warm to room temperature over night
  2. extractionextracted with 3×25 ml portions of methylene chloride
  3. washThe combined organic was washed with 2×10 ml portions water and 10 ml brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe resulting crude product was purified via silica gel chromatography on a 40 g Isco cartridge

Sources & evidence

ORD record
ord-bfcb64f110f34afa9e727051a21f330d
Source dataset
uspto-grants-2013_10
Patent number
US08552186B2

Reaction notes

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