Tetrahydrofuran → 4,4,6-Trifluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalene-1,2-diol

HRID 919193Notes

Reaction equation

HRID 919193 reaction equation
[CH2:1]1[CH2:5]OC[CH2:2]1.[Si]([O:13][CH:14]1[CH2:23][C:22]([F:25])([F:24])[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([F:26])[CH:20]=2)[C:15]1=[O:27])(C(C)(C)C)(C)C.F>N1C=CC=CC=1>[F:25][C:22]1([F:24])[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([F:26])[CH:20]=2)[C:15]([CH:1]([CH3:5])[CH3:2])([OH:27])[CH:14]([OH:13])[CH2:23]1

Participants

5

Reactant 3

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

Product 1

HCID 687469674,4,6-Trifluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalene-1,2-diolYield 69%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

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-509461a68bd144daabbf1563ce30ab56
Source dataset
uspto-grants-2016_03
Patent number
US09273009B2

Reaction notes

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