Hydrofluoric Acid → (S)-4,4,6-Trifluoro-1-isopropyl-3,4-dihydronaphthalen-2(1H)-one

HRID 2038353Notes

Reaction equation

HRID 2038353 reaction equation
[F:1][C:2]1([F:13])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[CH2:5][CH2:4][CH2:3]1.IN1C(=O)[CH2:18][CH2:17][C:16]1=O.F.FC1C=C2C(CCCC32SCCS3)=CC=1.S([O-])([O-])(=[O:40])=S.[Na+].[Na+]>ClCCl.N1C=CC=CC=1>[F:13][C:2]1([F:1])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[C@H:5]([CH:17]([CH3:18])[CH3:16])[C:4](=[O:40])[CH2:3]1

Participants

8

Reactant 5

HCID 14917Hydrofluoric AcidHCID 24477Sodium ThiosulfateHCID 120273N-IodosuccinimideHCID 584514381,1,7-Trifluoro-1,2,3,4-tetrahydronaphthaleneHCID 866652417'-Fluoro-3',4'-dihydro-2'H-spiro[[1,3]dithiolane-2,1'-naphthalene]

Product 1

HCID 58451445(S)-4,4,6-Trifluoro-1-isopropyl-3,4-dihydronaphthalen-2(1H)-oneYield 46%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-50 °C

Procedure

1,1,7-Trifluoro-1,2,3,4-tetrahydronaphthalene (52): A solution of N-iodosuccinimide (32.3 g, 144.0 mmol) in dichloromethane (260 mL) was cooled to −78° C. in a plastic round bottom flask. A 70% solution of hydrogen fluoride in pyridine (18 mL) followed by a dichloromethane solution (20 mL) of dithiolane 61 (8.65 g, 36.0 mmol) were added dropwise. Upon completion of addition the reaction was warmed to −50° C. and stirred at this temperature for 3 h. The reaction was then poured into ice cold saturated sodium bicarbonate (200 mL) followed by a saturated solution of sodium thiosulfate (150 mL). The colored reaction became colorless and biphasic. The organic phase was separated, dried (sodium sulfate) and concentrated to give a yellow oil. The product was purified by silica gel chromatography with a gradient heptanes/ethyl acetate eluent system on an ISCO companion system to give the desired product as a yellow oil (3.11 g, 16.7 mmol, 46% yield). 1H NMR (400 MHz, CDCl3) δ: 7.34 (d, J=8 Hz, 1H), 7.07 (m, 1H), 7.05 (m, 1H), 2.80 (brs, 2H), 2.26 (m, 2H), 1.99 (m, 2H); 19F NMR (400 MHz, CDCl3) δ: −91.7 (s, 2H), −122.8 (s, 1H).

Workup

  1. additionwere added dropwise
  2. additionUpon completion of addition the reaction
  3. customThe colored reaction
  4. customThe organic phase was separated
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated
  7. customto give a yellow oil
  8. customThe product was purified by silica gel chromatography with a gradient heptanes/ethyl acetate eluent system on an ISCO companion system

Sources & evidence

ORD record
ord-e008e0025ca44f3a8949ea72d82d7808
Source dataset
uspto-grants-2013_11
Patent number
US08575361B2

Reaction notes

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