Diisopropylamine → 5-(3-Benzyloxy-4-nitrobenzyl)-5,7,8,9-tetrahydrobenzocyclohepten-6-one

HRID 660709Notes

Reaction equation

HRID 660709 reaction equation
[CH:1](NC(C)C)(C)C.C([Li])CCC.[CH:13]1[C:18]2[CH2:19][CH2:20][CH2:21][C:22](=[O:24])[CH2:23][C:17]=2[CH:16]=[CH:15][CH:14]=1.[CH2:25]([O:32][C:33]1[CH:38]=[CH:37][C:36](CBr)=[CH:35][C:34]=1[N+:41]([O-:43])=[O:42])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1>[CH2:25]([O:32][C:33]1[CH:38]=[C:37]([CH:36]=[CH:35][C:34]=1[N+:41]([O-:43])=[O:42])[CH2:1][CH:23]1[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:18]=2[CH2:19][CH2:20][CH2:21][C:22]1=[O:24])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 124880816,7,8,9-tetrahydro-5H-benzo(7)annulen-6-oneHCID 233891491-Benzyloxy-4-bromomethyl-2-nitrobenzeneHCID 178418339Butyllithium

Product 1

HCID 688394335-(3-Benzyloxy-4-nitrobenzyl)-5,7,8,9-tetrahydrobenzocyclohepten-6-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of diisopropylamine (0.31 mL, 2.19 mmol) in THF (5 mL) at 0° C. is added n-butyllithium (1.6 M in hexane, 1.37 mL, 2.19 mmol) dropwise and the solution is stirred at 0° C. for 20 min then is cooled to −78° C. To this is added a solution of 5,7,8,9-tetrahydrobenzocyclohepten-6-one (J. Med. Chem. 40, 3516 (1997)) (350 mg, 2.19 mmol) in 2 THF is added dropwise. After one hour, a solution of 1-benzyloxy-4-bromomethyl-2-nitrobenzene (705 mg, 2.19 mmol) in THF (2 mL) is added dropwise and the mixture is allowed to warm to RT overnight. The mixture is quenched with saturated NaHCO3 and the solution is extracted with EtOAc. The organic layer is washed with water, brined and dried over MgSO4. The solvent is removed under reduced pressure and the residue is purified by flash chromatography using a gradient of 25-75% hexane/CH2Cl2 to give the title compound as a yellow liquid. 1H NMR (CDCl3): 7.72-7.70 (d, J=8.08 Hz, 1H), 7.42-7.11 (m, 8H), 6.92-6.90 (dd, J=1.27 Hz, 8.08 Hz, 1 H), 6.73-6.72 (m, 2H), 5.05-5.04 (d, J=2.78 Hz, 2H), 4.0-3.96 (t, J=7.08 Hz, 1H), 3.57-3.51 (q, J=7.58 Hz, 1H), 3.05-3.01 (q, J=6.06 Hz, 1H), 2.87-2.81 (m, 1H), 2.65-2.58 (m, 1H), 2.55-2.47 (m, 1H), 2.42-2.37 (m, 1H), 2.05-1.95 (m, 1H), 1.92-1.83 (m, 1H). (M−1)−=400.

Workup

  1. temperaturethen is cooled to −78° C
  2. additionis added dropwise
  3. waitAfter one hour
  4. temperatureto warm to RT overnight
  5. customThe mixture is quenched with saturated NaHCO3
  6. extractionthe solution is extracted with EtOAc
  7. washThe organic layer is washed with water
  8. dry with materialdried over MgSO4
  9. customThe solvent is removed under reduced pressure
  10. customthe residue is purified by flash chromatography

Sources & evidence

ORD record
ord-a4e02cac48234352aa460084db58be1f
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Reaction notes

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