Sodium Bicarbonate → Rac-6-[(4-tert-butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

HRID 1516700Notes

Reaction equation

HRID 1516700 reaction equation
Br[Mg][C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH3:12])([CH3:11])[CH3:10])=[CH:5][CH:4]=1.[F:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:29]([CH:30]=[O:31])=[C:28]([CH:32]([CH3:34])[CH3:33])[CH:27]=[C:26]3[C:21]=2[C:22](=[O:37])[CH2:23][C:24]([CH3:36])([CH3:35])[O:25]3)=[CH:16][CH:15]=1.C(=O)(O)[O-].[Na+]>O1CCCC1>[C:9]([C:6]1[CH:7]=[CH:8][C:3]([CH:30]([OH:31])[C:29]2[C:20]([C:17]3[CH:16]=[CH:15][C:14]([F:13])=[CH:19][CH:18]=3)=[C:21]3[C:26](=[CH:27][C:28]=2[CH:32]([CH3:34])[CH3:33])[O:25][C:24]([CH3:35])([CH3:36])[CH2:23][C:22]3=[O:37])=[CH:4][CH:5]=1)([CH3:12])([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 580030235-(4-Fluorophenyl)-7-isopropyl-2,2-dimethyl-4-oxochroman-6-carbaldehydeHCID 178440986HCID 178440986, compound

Product 1

HCID 58002954Rac-6-[(4-tert-butylphenyl)(hydroxy)methyl]-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

At −78° C., 2.12 ml (1.06 mmol) of a freshly prepared 0.5 M solution of bromo(4-tert-butylphenyl)magnesium in tetrahydrofuran are slowly added dropwise to a solution of 300 mg (880 μmol) of 5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-4-oxochroman-6-carbaldehyde (Example 20A) in 7 ml of tetrahydrofuran. The mixture is then allowed to thaw slowly to −20° C. and stirred at this temperature for 45 min. 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, the solvent is then removed under reduced pressure and the residue is purified by column chromatography on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 10:1).

Workup

  1. customthaw slowly to −20° C.
  2. extractionthe mixture is extracted three times with ethyl acetate
  3. washthe combined organic phases are washed with saturated sodium chloride solution
  4. dry with materialThe organic phases are dried over magnesium sulfate
  5. customthe solvent is then removed under reduced pressure
  6. customthe residue is purified by column chromatography on silica gel (mobile phase: gradient cyclohexane→cyclohexane/ethyl acetate 10:1)

Sources & evidence

ORD record
ord-7ff54fda94f84d70b9249d20bb954d14
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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