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

HRID 1516697Notes

Reaction equation

HRID 1516697 reaction equation
Br[Mg][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=1.[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:30]([CH:31]=[O:32])=[C:29]([CH:33]([CH3:35])[CH3:34])[CH:28]=[C:27]3[C:22]=2[C:23](=[O:38])[CH2:24][C:25]([CH3:37])([CH3:36])[O:26]3)=[CH:17][CH:16]=1.FC1C=CC(C2C(C=O)=C(CCC)C=C3C=2C(=O)CC(C)(C)O3)=CC=1.C(=O)(O)[O-].[Na+]>O1CCCC1>[F:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[C:30]([CH:31]([OH:32])[C:3]3[CH:8]=[CH:7][C:6]([O:9][C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=3)=[C:29]([CH:33]([CH3:34])[CH3:35])[CH:28]=[C:27]3[C:22]=2[C:23](=[O:38])[CH2:24][C:25]([CH3:36])([CH3:37])[O:26]3)=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 580030235-(4-Fluorophenyl)-7-isopropyl-2,2-dimethyl-4-oxochroman-6-carbaldehydeHCID 87679748Rac-5-(4-fluorophenyl)-7-n-propyl-2,2-dimethyl-4-oxochroman-6-carbaldehydeHCID 178506384HCID 178506384, compound

Product 1

HCID 58002959Rac-5-(4-fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropyl-2,2-dimethyl-2,3-dihydro-4h-chromen-4-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

At −78° C., 2.35 ml (1.19 mmol) of a freshly prepared 0.5 M solution of bromo[4-(trifluoromethoxy)phenyl]magnesium in tetrahydrofuran are slowly added dropwise to a solution of 338 mg (990 μmol) of a 2:1 mixture of rac-5-(4-fluorophenyl)-7-isopropyl-2,2-dimethyl-4-oxochroman-6-carbaldehyde (Example 20A) and rac-5-(4-fluorophenyl)-7-n-propyl-2,2-dimethyl-4-oxochroman-6-carbaldehyde in 8 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 preparative HPLC (method 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 preparative HPLC (method 1)

Sources & evidence

ORD record
ord-fd1be789860f412bb0e4e67410f33afd
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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