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

HRID 2038355Notes

Reaction equation

HRID 2038355 reaction equation
[F:1][C:2]1([F:18])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([F:12])[CH:10]=2)[C:5]([CH:14]([CH3:16])[CH3:15])(O)[CH:4]([OH:17])[CH2:3]1.C1COCC1.[Si](OC1CC(F)(F)C2C(=CC=C(F)C=2)C1=O)(C(C)(C)C)(C)C.F>N1C=CC=CC=1>[F:18][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:14]([CH3:16])[CH3:15])[C:4](=[O:17])[CH2:3]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14917Hydrofluoric AcidHCID 687469674,4,6-Trifluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalene-1,2-diolHCID 687481142-((tert-Butyldimethylsilyl)oxy)-4,4,6-trifluoro-3,4-dihydronaphthalen-1(2H)-one

Product 1

HCID 58451445(S)-4,4,6-Trifluoro-1-isopropyl-3,4-dihydronaphthalen-2(1H)-oneYield 69%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

4,4,6-Trifluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalene-1,2-diol (62): A THF solution (8 mL) of 2-((tert-butyldimethylsilyl)oxy)-4,4,6-trifluoro-3,4-dihydronaphthalen-1(2H)-one 54 (0.585 g, 1.77 mmol) was cooled to 0° C. and a solution of hydrogen fluoride in pyridine (70%, 200 μL) was added dropwise. The reaction was allowed to warm to ambient temperature over 12 h at which point the reaction was quenched with an aqueous solution of saturated sodium bicarbonate, volatiles were removed and the mixture was re-dissolved in ethyl acetate. The aqueous phase was extracted with ethyl acetate (3×), dried over sodium sulfate, filtered and concentrated to give an orange oil. The desired product, 4,4,6-trifluoro-2-hydroxy-3,4-dihydronaphthalen-1(2H)-one, was purified with a gradient heptanes/ethyl acetate eluent system on silica gel by a ISCO companion system to give the desired product as a colorless oil (0.263 g, 1.22 mmol, 69% yield). 1H NMR (400 MHz, CDCl3) δ: 8.14 (dd, J=8, 4 Hz, 1H), 7.48 (dt, J=8, 4 Hz, 1H), 7.36 (m, 1H), 4.67 (ddd, J=12, 8, 4 Hz, 1H), 3.66 (s, 1H), 3.17 (m, 1H), 2.54 (m, 1H).

Workup

  1. customwas quenched with an aqueous solution of saturated sodium bicarbonate, volatiles
  2. customwere removed
  3. dissolutionthe mixture was re-dissolved in ethyl acetate
  4. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give an orange oil
  9. customThe desired product, 4,4,6-trifluoro-2-hydroxy-3,4-dihydronaphthalen-1(2H)-one, was purified with a gradient heptanes/ethyl acetate eluent system on silica gel by a ISCO companion system

Sources & evidence

ORD record
ord-11765bb118794bfabe65afa4fd398c6a
Source dataset
uspto-grants-2013_11
Patent number
US08575361B2

Reaction notes

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