Diisopropylamine → HCID 21929097, compound

HRID 1243848Notes

Reaction equation

HRID 1243848 reaction equation
[N+:1](=[CH:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])=[N-:2].[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH2:21][CH2:20][C:19](=O)[CH:18]=[CH:17]2)=[CH:12][CH:11]=1.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.C(NC(C)C)(C)C>O1CCCC1.C(OCC)(=O)C.C(O)(=O)C>[F:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2([C:23]3[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=3)[CH2:17][C:18]3[NH:2][N:1]=[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:19]=3[CH:20]=[CH:21]2)=[CH:14][CH:15]=1

Participants

9

Reactant 5

HCID 7912DiisopropylamineHCID 12192Ethyl diazoacetateHCID 2724682Lithium diisopropylamideHCID 219287994,4-Bis(4-fluorophenyl)cyclohex-2-enoneHCID 178418339Butyllithium

Product 1

HCID 21929097HCID 21929097, compound

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-70 °C

Procedure

1.4 cm3 of ethyl diazoacetate are added dropwise to a solution, cooled to −70° C., of 3 g of 4,4-bis(4-fluorophenyl)cyclohex-2-enone in 75 cm3 of tetrahydrofuran, followed by slow addition of 37.9 cm3 of lithium diisopropylamide solution prepared from 10.5 cm3 of 1.6 M n-butyllithium and 2.4 cm3 of diisopropylamine in solution in 25 cm3 of tetrahydrofuran. After stirring the reaction mixture at a temperature in the region of −70° C. for 3 hours, 1.9 cm3 of glacial acetic acid are added and the temperature is allowed to rise to the region of 20° C. 250 cm3 of ethyl acetate are added and the organic phases are then washed with twice 150 cm3 of distilled water, dried over sodium sulphate and concentrated to dryness under reduced pressure. The residue is dissolved in 100 cm3 of toluene and heated at a temperature in the region of 110° C. for 3 hours and then concentrated to dryness under reduced pressure. The residue obtained is purified by flash chromatography on silica gel (35–70 μm), eluting with a dichloromethane/diisopropyl ether (50/50) mixture; 1.2 g of ethyl 6,6-bis(4-fluorophenyl)-6,7-dihydro-1H-indazole-3-carboxylate are thus obtained in the form of a beige-coloured foam, the characteristics of which are as follows:

Workup

  1. customto rise to the region of 20° C
  2. washthe organic phases are then washed with twice 150 cm3 of distilled water
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated to dryness under reduced pressure
  5. dissolutionThe residue is dissolved in 100 cm3 of toluene
  6. temperatureheated at a temperature in the region of 110° C. for 3 hours
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe residue obtained
  9. customis purified by flash chromatography on silica gel (35–70 μm)
  10. washeluting with a dichloromethane/diisopropyl ether (50/50) mixture

Sources & evidence

ORD record
ord-ee0e9e58265a4df2965332d240eee2c5
Source dataset
uspto-grants-2006_10
Patent number
US07119115B2

Reaction notes

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