4,4,6-trifluoro-2-hydroxy-3,4-dihydronaphthalen-1(2H)-one → 4,4,6-Trifluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalene-1,2-diol

HRID 919194Notes

Reaction equation

HRID 919194 reaction equation
C[Li].[CH:3]([Mg]Cl)([CH3:5])[CH3:4].[F:8][C:9]1([F:22])[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:19])[CH:17]=2)[C:12](=[O:20])[CH:11]([OH:21])[CH2:10]1>C1COCC1>[F:22][C:9]1([F:8])[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([F:19])[CH:17]=2)[C:12]([CH:3]([CH3:5])[CH3:4])([OH:20])[CH:11]([OH:21])[CH2:10]1

Participants

5

Reactant 3

HCID 687488174,4,6-trifluoro-2-hydroxy-3,4-dihydronaphthalen-1(2H)-oneHCID 178418348HCID 178418348, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 687469674,4,6-Trifluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalene-1,2-diol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A THF solution (3.75 mL) of methyl lithium (3.05 mL, 4.88 mmol) was cooled to −78° C. with a dry ice/acetone cooling bath. A hexanes solution of isopropyl magnesium chloride (1.44 mL, 2.68 mmol) was introduced by syringe. This mixture was allowed to age for one hour at this temperature. Then a THF solution (1.75 mL) of 4,4,6-trifluoro-2-hydroxy-3,4-dihydronaphthalen-1(2H)-one (0.263 mg, 1.22 mmol) was added to the cooled solution dropwise by syringe pump over one hour. The reaction was allowed to stir at −78° C. for 4 hours and then quenched by pouring into an aqueous solution of ammonium chloride, 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, 4,4,6-trifluoro-1-isopropyl-1,2,3,4-tetrahydronaphthalene-1,2-diol, as a colorless oil (0.189 g, 0.727 mmol, 60% yield). 1H NMR (400 MHz, CDCl3) δ: 7.65 (m, 1H), 7.34 (d, J=8 Hz, 1H), 7.19 (m, 1H), 4.32 (m, 1H), 2.69 (m, 2H), 1.96 (q, J=8 Hz, 1H) 0.98 (d, J=4 Hz, 1H) 0.93 (d, J=4 Hz, 1H). MS (ESI−, infusion) 259 [(M−H)−].

Workup

  1. customquenched
  2. additionby pouring into an aqueous solution of ammonium chloride, volatiles
  3. customwere removed
  4. dissolutionthe mixture was re-dissolved in ethyl acetate
  5. extractionThe aqueous phase was extracted with ethyl acetate (3×)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give an orange oil
  10. 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-7cc388b857e8410487fd9498521b5f77
Source dataset
uspto-grants-2016_03
Patent number
US09273009B2

Reaction notes

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