Ethanol → Ethyl-4-(spiro[indene-1,4'-piperidine]-1'-ylmethyl)benzoate

HRID 390392

Reaction equation

HRID 390392 reaction equation
Br[CH2:2][C:3]1[CH:13]=[CH:12][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][CH:4]=1.C([N:17]([CH:20]([CH3:22])C)[CH2:18][CH3:19])(C)C.[CH2:23](O)[CH3:24]>>[CH2:10]([O:9][C:7](=[O:8])[C:6]1[CH:12]=[CH:13][C:3]([CH2:2][N:17]2[CH2:18][CH2:19][C:23]3([C:24]4[C:5](=[CH:4][CH:3]=[CH:13][CH:12]=4)[CH:6]=[CH:7]3)[CH2:22][CH2:20]2)=[CH:4][CH:5]=1)[CH3:11]

Participants

4

Reactant 3

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 954261Ethyl 4-(bromomethyl)benzoate

Product 1

HCID 58230576Ethyl-4-(spiro[indene-1,4'-piperidine]-1'-ylmethyl)benzoateYield 60%

Conditions

Temperature
85 °C

Procedure

To a solution of spiro-[indene-1,4-piperidine]trifluoroacetate (4 g, 14 mmol) in ethanol (25 mL) is added ethyl 4-(bromomethyl)-benzoate (2.9 g, 12.6 mmol), followed by diisopropylethylamine (9.6 mL, 56 mmol). The reaction mixture is refluxed at 85° C. for overnight. The ethanol is removed under reduced pressure and the residue is partitioned between EtOAc (150 mL) and water (50 mL). The organic layer is washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography, eluting with hexane:ethyl acetate (8.0:2.0) to give the title compound as brown solid (2.8 g, 60%). 1H NMR (400 MHz) 7.94 (d, J=8 Hz, 2H), 7.51 (d, J=8 Hz, 2H), 7.43 (d, J=7.2 Hz, 1H), 7.31 (d, J=7.2 Hz, 1H), 7.18 (m, J=7.2 Hz, 2H), 6.94 (d, J=5.6 Hz, 1H), 6.78 (d, J=5.6 Hz, 1H), 4.30 (q, J=7.2 Hz, 2H), 3.67 (s, 2H), 2.85 (d, J=11.6 Hz, 2H), 2.38 (t, J=11.6 Hz, 2H), 2.09 (t, J=10.4 Hz, 2H), 1.31 (t, J=7.2 Hz, 2H), 1.19 (d, J=12.8 Hz, 2H).

Workup

  1. customThe ethanol is removed under reduced pressure
  2. customthe residue is partitioned between EtOAc (150 mL) and water (50 mL)
  3. washThe organic layer is washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is purified by silica gel chromatography
  8. washeluting with hexane:ethyl acetate (8.0:2.0)

Sources & evidence

ORD record
ord-6c4aa83c8d2c4cffbab02671451f0b35
Source dataset
uspto-grants-2013_02
Patent number
US08383642B2

Linked notes

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