Ethyl ketone → 2,2-Diethyl-6-fluorochroman-4-one

HRID 1911267Notes

Reaction equation

HRID 1911267 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[CH3:12][CH2:13][C:14](=O)[CH2:15][CH3:16].N1CCCC1>CO>[CH2:13]([C:14]1([CH2:15][CH3:16])[CH2:9][C:8](=[O:10])[C:6]2[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:7]=2)[O:11]1)[CH3:12]

Participants

5

Reactant 3

HCID 7288Ethyl ketoneHCID 31268PyrrolidineHCID 959922-Acetyl-4-fluorophenol

Product 1

HCID 673626752,2-Diethyl-6-fluorochroman-4-oneYield 89.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

1-(5-Fluoro-2-hydroxyphenyl)ethanone (30.2 g, 196 mmol) and MeOH (300 mL) were stirred at ambient temperature and 3-pentanone (41.6 mL, 392 mmol) and pyrrolidine (17.8 mL, 216 mmol) were added. The mixture was heated to 60° C. for 62 h at which point LCMS analysis showed clean conversion to product. The reaction was cooled, concentrated to a minimal volume of MeOH, and MTBE (300 mL) was added. The organics were washed with 2N HCl (150 mL), brine (60 mL), 2N NaOH (150 mL), and brine (60 mL). The solution was passed through a plug of silica gel (30 g), washing with MTBE (150 mL). The filtrate was concentrated, giving the title compound (38.8 g, 175 mmol, 89%) as a light brown oil. MS (DCI/NH3) m/z 240 (M+NH4)+.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated to a minimal volume of MeOH, and MTBE (300 mL)
  3. additionwas added
  4. washThe organics were washed with 2N HCl (150 mL), brine (60 mL), 2N NaOH (150 mL), and brine (60 mL)
  5. washwashing with MTBE (150 mL)
  6. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-51062516742a4ef6af8b5acf8986f8da
Source dataset
uspto-grants-2013_12
Patent number
US08604053B2

Reaction notes

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