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

HRID 1516717Notes

Reaction equation

HRID 1516717 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:38])([F:37])[C:29]1[CH:34]=[CH:33][C:32]([Mg]Br)=[CH:31][CH:30]=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:32]3[CH:33]=[CH:34][C:29]([C:28]([F:38])([F:37])[F:27])=[CH:30][CH:31]=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 178506198HCID 178506198, compound

Product 1

HCID 580030305-(4-Fluorophenyl)-6-{hydroxy[4-(trifluoromethyl)phenyl]methyl}-7-isopropylspiro[chromen-2,1'-cyclobutan]-4(3H)-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Under argon, 0.70 g (1.99 mmol) of 5-(4-fluorophenyl)-7-isopropyl-4-oxo-3,4-dihydrospiro-[chromen-2,1′-cyclobutane]-6-carbaldehyde (Example 51A) is suspended in 30 ml of tetrahydrofuran and cooled to −78° C. 5.25 ml (2.62 mmol) of a freshly prepared 0.5 M solution of [4-(trifluoromethyl)phenyl]magnesium bromide in tetrahydrofuran are added slowly. The mixture is stirred briefly at −78° C. and then warmed to 0° C. After about 30 min, 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 a little at a time by preparative HPLC (method 12). This gives 0.635 g (64% of theory) of the title compound.

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 a little at a time by preparative HPLC (method 12)

Sources & evidence

ORD record
ord-2812ab64ae98406e9d3e905682a52e5a
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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