HCID 86618069, compound → HCID 59429093, compound

HRID 1644151Notes

Reaction equation

HRID 1644151 reaction equation
[CH3:1][Mg]Br.C[C:5]1([C:12]([OH:21])([C:17]([F:20])([F:19])[F:18])[C:13]([F:16])([F:15])[F:14])[CH2:10][CH2:9][CH2:8][CH2:7][C:6]1=[O:11]>O1CCCC1>[F:20][C:17]([F:18])([F:19])[C:12]([CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C:6]1([CH3:1])[OH:11])([OH:21])[C:13]([F:15])([F:14])[F:16]

Participants

4

Reactant 2

HCID 86618069HCID 86618069, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 59429093HCID 59429093, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a flame-dried, nitrogen-purged, 250 mL 3-neck roundbottom flask with 50 mL, pressure-equalized addition funnel and stirbar was added 48 mL of methyl magnesium bromide (143 mmol, 2.1 eq., 3 M in ethyl ether). A degassed solution of 18 g methyl 2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)cyclohexanone (IX) (68 mmol, 1 eq.) in 60 mL anhydrous tetrahydrofuran was charged to the addition funnel and added dropwise to the reaction over the course of 1 hour at room temperature. The reaction was stirred at room temperature for 14 hours, after which it was cooled to 0° C. and carefully quenched with dilute hydrochloric acid solution until the pH was less than 5.0. The reaction solution was neutralized with saturated aqueous sodium bicarbonate until the pH was greater than 8. The product was extracted into ethyl ether and the organic phase washed with brine and dried over magnesium sulfate, filtered, concentrated in vacuo, and stored over a small amount of sodium bicarbonate. Crude .sup.1H and .sup.19F NMR indicated only 42% conversion to a single isomer. The reaction was repeated again and the conversion driven to 69% by NMR. The crude product was taken on to the next step without further purification.

Workup

  1. customTo a flame-dried, nitrogen-purged
  2. additionadded dropwise to the reaction over the course of 1 hour at room temperature
  3. temperatureafter which it was cooled to 0° C.
  4. customcarefully quenched with dilute hydrochloric acid solution until the pH was less than 5.0
  5. extractionThe product was extracted into ethyl ether
  6. washthe organic phase washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was taken on to the next step without further purification

Sources & evidence

ORD record
ord-95f2d987d1ad4013ae45f4aae761331a
Source dataset
uspto-grants-2012_02
Patent number
US08124327B2

Reaction notes

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