Sulfuric Acid → 6-Fluoro-1,2,3,4-tetrahydronaphthalen-1-one

HRID 2201623Notes

Reaction equation

HRID 2201623 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][CH2:10][C:11]([OH:13])=O)[CH:5]=[CH:6][CH:7]=1.S(=O)(=O)(O)O>>[F:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][CH:7]=1)[C:11](=[O:13])[CH2:10][CH2:9][CH2:8]2

Participants

3

Reactant 2

HCID 1118Sulfuric AcidHCID 149151134-(3-Fluorophenyl)butanoic acid

Product 1

HCID 149151166-Fluoro-1,2,3,4-tetrahydronaphthalen-1-oneYield 73.9%

Conditions

Temperature
45 °C

Procedure

Crude 4-(3-fluorophenyl)butyric acid (8.83 kg) was added to concentrated sulfuric acid (30 kg) in a chemical reactor at a rate such that the pot temperature stayed between 40° C. and 60° C. (jacket heating was not necessary). The reaction was stirred at 45° C. for 3 hours and reaction completion was confirmed by LC. The reaction mixture was cooled and quenched with water (16 L), and then extracted with 35% THF in methylene chloride (25.8 kg). The organic layer was separated and washed with water (16 L), saturated aqueous NaHCO3 (16.9 kg) and then a mixture of water (16.1-kg)/brine (4.7-kg). The organic later was concentrated under vacuum and re-stripped with the aid of hexane to remove water and afford 6-fluoro-3,4-dihydro-2H-naphthalen-1-one as an oil (5.88 kg): MS (M+1)=165; H1 NMR (300 MHz): δ ppm (CDCl3): 2.14 (2H, m, J=6.03, 5.75 Hz), 2.64 (2H, dd, J=6.03, 5.75 Hz); 2.94 (2H, t, J=6.03), 6.9-7.0 (2H, m, J=2.26, 2.64, 6.03 Hz), 8.02-8.07 (1H, dd, J=6.03).

Workup

  1. customstayed between 40° C. and 60° C.
  2. temperatureheating
  3. customreaction completion
  4. temperatureThe reaction mixture was cooled
  5. customquenched with water (16 L)
  6. extractionextracted with 35% THF in methylene chloride (25.8 kg)
  7. customThe organic layer was separated
  8. washwashed with water (16 L), saturated aqueous NaHCO3 (16.9 kg)
  9. additiona mixture of water (16.1-kg)/brine (4.7-kg)
  10. concentrationThe organic later was concentrated under vacuum and re-stripped with the aid of hexane
  11. customto remove water

Sources & evidence

ORD record
ord-d55e23fe281949d382b29d09e2c356d5
Source dataset
uspto-grants-2016_06
Patent number
US09365494B2

Reaction notes

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