Diisopropylamine → 3-(4-Propylbenzoyl)-7-vinylchroman-4-one

HRID 1506315Notes

Reaction equation

HRID 1506315 reaction equation
C([Li])CCC.C(NC(C)C)(C)C.[CH:13]([C:15]1[CH:24]=[C:23]2[C:18]([C:19](=[O:25])[CH2:20][CH2:21][O:22]2)=[CH:17][CH:16]=1)=[CH2:14].[CH2:26]([C:29]1[CH:37]=[CH:36][C:32]([C:33](F)=[O:34])=[CH:31][CH:30]=1)[CH2:27][CH3:28]>C1COCC1>[CH2:26]([C:29]1[CH:30]=[CH:31][C:32]([C:33]([CH:20]2[C:19](=[O:25])[C:18]3[C:23](=[CH:24][C:15]([CH:13]=[CH2:14])=[CH:16][CH:17]=3)[O:22][CH2:21]2)=[O:34])=[CH:36][CH:37]=1)[CH2:27][CH3:28]

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 22323781HCID 22323781, compoundHCID 872945534-Propylbenzoyl fluorideHCID 178418339Butyllithium

Product 1

HCID 671683203-(4-Propylbenzoyl)-7-vinylchroman-4-oneYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a flame-dried 10 mL round-bottom flask under nitrogen charged with butyllithium (2.5 M in hexanes) (0.875 mL, 2.19 mmol) in THF (1 mL) at 0° C. was added diisopropylamine (0.312 mL, 2.19 mmol) dropwise. The solution was stirred at 0° C. for 20 min. The solution was then cooled to −78° C., and 7-vinylchroman-4-one (Preparation 2D, 1.79 M in THF) (1.02 mL, 1.82 mmol) was added dropwise via syringe. The mixture was stirred for 20 min. at −78° C. 4-propylbenzoyl fluoride (0.303 g, 1.823 mmol) in 1 mL of THF was then added dropwise via syringe, and the reaction mixture was stirred at −78° C. for 60 min. and then warmed to room temperature. The reaction was quenched with 1N aqueous hydrochloric acid (5 mL) and extracted with ethyl acetate (3×20 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The yellow residue was purified by flash silica gel chromatography using a mixture of ethyl acetate in hexane (5%-12%) to give 3-(4-propylbenzoyl)-7-vinylchroman-4-one (0.179 g, 0.559 mmol, 31% yield). The compound was triturated with methanol with sonication, filtered, washed with methanol, and dried to give 3-(4-propylbenzoyl)-7-vinylchroman-4-one (0.125 g, 0.390 mmol, 21% yield) as a yellow solid. LC/MS M+1=321.2. 1H NMR (500 MHz, DMSO-d6) δ ppm 0.91 (t, 3H), 1.58-1.68 (m, J=7.42, 7.42, 7.42, 7.42, 7.21 Hz, 2H), 2.65 (t, J=7.63 Hz, 2H) 4.71-4.77 (m, 1H), 4.78-4.83 (m, 1H), 5.20 (dd, J=9.16, 4.99 Hz, 1H), 5.47 (d, J=11.10 Hz, 1H), 6.05 (d, J=17.76 Hz, 1H), 6.73-6.82 (m, 1H), 7.17 (s, 1H) 7.24 (dd, J=8.18, 1.25 Hz, 1H), 7.38 (d, J=8.32 Hz, 2H), 7.73 (d, J=8.05 Hz, 1H), and 7.96 (d, J=8.32 Hz, 2H).

Workup

  1. temperatureThe solution was then cooled to −78° C.
  2. stirringThe mixture was stirred for 20 min. at −78° C
  3. stirringthe reaction mixture was stirred at −78° C. for 60 min.
  4. temperaturewarmed to room temperature
  5. customThe reaction was quenched with 1N aqueous hydrochloric acid (5 mL)
  6. extractionextracted with ethyl acetate (3×20 mL)
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe yellow residue was purified by flash silica gel chromatography
  11. additiona mixture of ethyl acetate in hexane (5%-12%)

Sources & evidence

ORD record
ord-216547032feb4832bea052b57d15bf00
Source dataset
uspto-grants-2015_12
Patent number
US09216972B2

Reaction notes

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