Sodium Bicarbonate → 5-(4-Fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

HRID 1516722Notes

Reaction equation

HRID 1516722 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:20]([CH:21]=[O:22])=[C:19]([CH:23]([CH3:25])[CH3:24])[CH:18]=[C:17]3[C:9]=2[C:10](=[O:26])[CH2:11][C:12]2([O:16]3)[CH2:15][CH2:14][CH2:13]2)=[CH:4][CH:3]=1.[F:27][C:28]([F:39])([F:38])[O:29][C:30]1[CH:35]=[CH:34][C:33]([Mg]Br)=[CH:32][CH:31]=1.C(=O)(O)[O-].[Na+]>O1CCCC1.O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:20]([CH:21]([OH:22])[C:33]3[CH:32]=[CH:31][C:30]([O:29][C:28]([F:27])([F:38])[F:39])=[CH:35][CH:34]=3)=[C:19]([CH:23]([CH3:24])[CH3:25])[CH:18]=[C:17]3[C:9]=2[C:10](=[O:26])[CH2:11][C:12]2([O:16]3)[CH2:15][CH2:14][CH2:13]2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 580030415-(4-Fluorophenyl)-7-isopropyl-4-oxo-3,4-dihydrospiro[chromen-2,1'-cyclobutane]-6-carbaldehydeHCID 178506384HCID 178506384, compound

Product 1

HCID 580029385-(4-Fluorophenyl)-6-{hydroxy[4-(trifluoromethoxy)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

Under argon, 0.60 g (1.70 mmol) of 5-(4-fluorophenyl)-7-isopropyl-4-oxo-3,4-dihydrospiro-[chromen-2,1′-cyclobutane]-6-carbaldehyde (Example 51A) is suspended in 15 ml of tetrahydrofuran and cooled to −70° C. 4.3 ml (2.13 mmol) of a freshly prepared 0.5 M solution of [4-(trifluoromethoxy)phenyl]magnesium bromide in tetrahydrofuran are added slowly. The mixture is stirred briefly at −78° C. and then warmed to 0° C. After 1 h, the mixture is hydrolyzed with sodium bicarbonate solution, diluted with water and 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 purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 25:1→10:1). This gives 710 mg (81% of theory) of the title compound in a purity of 70%.

Workup

  1. temperaturewarmed to 0° C
  2. extractionextracted repeatedly with ethyl acetate
  3. washThe combined organic phases are washed twice with saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product is purified on a silica gel column (mobile phase: cyclohexane/ethyl acetate 25:1→10:1)

Sources & evidence

ORD record
ord-dd100a6f72c84fe59c25999e84bb1d9d
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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