Sodium Bicarbonate → HCID 58002993, compound

HRID 1516685Notes

Reaction equation

HRID 1516685 reaction equation
[CH:1]1([C:6]2[CH:15]=[C:14]3[C:9]([C:10](=[O:18])[CH2:11][C:12]([CH3:17])([CH3:16])[O:13]3)=[C:8]([O:19][CH3:20])[C:7]=2[CH:21]=[O:22])[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[Mg][C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=1.C(=O)(O)[O-].[Na+]>O1CCCC1>[CH:1]1([C:6]2[CH:15]=[C:14]3[C:9]([C:10](=[O:18])[CH2:11][C:12]([CH3:17])([CH3:16])[O:13]3)=[C:8]([O:19][CH3:20])[C:7]=2[CH:21]([OH:22])[C:25]2[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 58003009HCID 58003009, compoundHCID 178506198HCID 178506198, compound

Product 1

HCID 58002993HCID 58002993, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under argon, 3.7 g (12.24 mmol) of 7-cyclopentyl-5-methoxy-2,2-dimethyl-4-oxochroman-6-carbaldehyde (Example 6A) are suspended in 150 ml of tetrahydrofuran and cooled to −78° C. 29.4 ml (14.68 mmol) of a freshly prepared 0.5 M solution of bromo[4-(trifluoro-methyl)phenyl]magnesium in tetrahydrofuran are added slowly. The mixture is then warmed to −20° C. and stirred at this temperature for 30 min. At −20° C., another 12.3 ml (6.15 mmol) of the above Grignard solution are added, and the mixture is stirred for a further 45 min. The mixture is then hydrolyzed using 5% strength sodium bicarbonate solution and then extracted repeatedly with ethyl acetate. The combined organic phases are washed twice with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The crude product is chromatographed on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1→2:1). This gives 2.35 g (43% of theory) of the title compound.

Workup

  1. temperatureThe mixture is then warmed to −20° C.
  2. additionAt −20° C., another 12.3 ml (6.15 mmol) of the above Grignard solution are added
  3. stirringthe mixture is stirred for a further 45 min
  4. extractionextracted repeatedly with ethyl acetate
  5. washThe combined organic phases are washed twice with saturated sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product is chromatographed on silica gel (mobile phase: cyclohexane/ethyl acetate 20:1→2:1)

Sources & evidence

ORD record
ord-9347d261fa274a548974f3b5dd690869
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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