Sodium Bicarbonate → 5-Cyclohex-1-en-1-yl-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one

HRID 1516706Notes

Reaction equation

HRID 1516706 reaction equation
Br[Mg][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][CH:4]=1.[C:13]1([C:19]2[C:28]([CH:29]=[O:30])=[C:27]([CH:31]([CH3:33])[CH3:32])[CH:26]=[C:25]3[C:20]=2[C:21](=[O:36])[CH2:22][C:23]([CH3:35])([CH3:34])[O:24]3)[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]=1.C(=O)(O)[O-].[Na+]>O1CCCC1>[C:13]1([C:19]2[C:28]([CH:29]([OH:30])[C:3]3[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][CH:4]=3)=[C:27]([CH:31]([CH3:32])[CH3:33])[CH:26]=[C:25]3[C:20]=2[C:21](=[O:36])[CH2:22][C:23]([CH3:34])([CH3:35])[O:24]3)[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 580029485-Cyclohex-1-en-1-yl-7-isopropyl-2,2-dimethyl-4-oxochroman-6-carbaldehydeHCID 178506198HCID 178506198, compound

Product 1

HCID 580029855-Cyclohex-1-en-1-yl-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

At −78° C., 2.03 ml (1.02 mmol) of a freshly prepared 0.5 M solution of bromo[4-(trifluoromethyl)phenyl]magnesium in tetrahydrofuran are slowly added dropwise to a solution of 255 mg (780 μmol) of 5-cyclohex-1-en-1-yl-7-isopropyl-2,2-dimethyl-4-oxochroman-6-carbaldehyde (Example 33A) in 6 ml of tetrahydrofuran. The mixture is then allowed to thaw slowly to −20° C. and stirred at this temperature for 45 min. A further 300 μl (193 μmol) of the above Grignard solution are added and stirring is continued for a further hour, the solution slowly thawing to 0° C. 10% strength sodium bicarbonate solution is then added, the mixture is extracted three times with ethyl acetate and the combined organic phases are washed with saturated sodium chloride solution. The organic phases are dried over magnesium sulfate and the solvent is then removed under reduced pressure. The residue is dissolved in a mixture of cyclohexane and ethyl:acetate (10:1), whereupon the target product crystallizes and is filtered off. The filtrate is concentrated and the residue is purified by column chromatography on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 20:1→10:1). The resulting target product is combined with the crystals. The compound is present in the form of atropisomers (1:1).

Workup

  1. customthaw slowly to −20° C.
  2. additionA further 300 μl (193 μmol) of the above Grignard solution are added
  3. stirringstirring
  4. waitis continued for a further hour
  5. customto 0° C
  6. extractionthe mixture is extracted three times with ethyl acetate
  7. washthe combined organic phases are washed with saturated sodium chloride solution
  8. dry with materialThe organic phases are dried over magnesium sulfate
  9. customthe solvent is then removed under reduced pressure
  10. dissolutionThe residue is dissolved in a mixture of cyclohexane and ethyl:acetate (10:1), whereupon the target product
  11. customcrystallizes
  12. filtrationis filtered off
  13. concentrationThe filtrate is concentrated
  14. customthe residue is purified by column chromatography on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 20:1→10:1)

Sources & evidence

ORD record
ord-887b2d7e56d848c084ff293836e48a72
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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