Ammonium Chloride → 7-Cyclopentyl-5-hydroxyspiro[chromen-2,1'-cyclobutan]-4(3H)-one

HRID 1516714Notes

Reaction equation

HRID 1516714 reaction equation
FC(F)(F)S(O[C:7]1[CH:19]=[C:18]2[C:10]([C:11](=[O:20])[CH2:12][C:13]3([O:17]2)[CH2:16][CH2:15][CH2:14]3)=[C:9]([OH:21])[CH:8]=1)(=O)=O.[Cl-].[Li+].[Br-].[CH:27]1([Zn+])[CH2:31][CH2:30][CH2:29][CH2:28]1.[Cl-].[NH4+]>O.Cl.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C)C=O>[CH:27]1([C:7]2[CH:19]=[C:18]3[C:10]([C:11](=[O:20])[CH2:12][C:13]4([O:17]3)[CH2:16][CH2:15][CH2:14]4)=[C:9]([OH:21])[CH:8]=2)[CH2:31][CH2:30][CH2:29][CH2:28]1

Participants

10

Reactant 4

HCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 58002968HCID 58002968, compoundHCID 178419768HCID 178419768, compound

Product 1

HCID 580029377-Cyclopentyl-5-hydroxyspiro[chromen-2,1'-cyclobutan]-4(3H)-one

Reagents, catalysts & solvents 5

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Under argon, 8.45 g (24.0 mmol) of 5-hydroxy-4-oxo-3,4-dihydrospiro[chromen-2,1′-cyclobutan]-7-yl trifluoromethanesulfonate (Example 44A), 3.92 g (4.8 mmol) of [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) and 6.10 g (144.0 mmol) of lithium chloride are suspended in 250 ml of abs. dimethylformamide. The mixture is cooled to 0° C., 216 ml (108 mmol) of (cyclopentyl)zinc bromide (0.5 M solution in tetrahydrofuran) are added and the mixture is stirred at room temperature overnight. Saturated ammonium chloride solution is then added to the mixture. The mixture is diluted with water, 1 N hydrochloric acid and ethyl acetate, the organic phase is separated off and the aqueous phase is extracted repeatedly with ethyl actate. The combined organic phases are washed twice with water and once with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue is adsorbed on silica gel and purified on a silica gel column (mobile phase: cyclohexane→cyclohexane/ethyl acetate 10:1). This gives 6.2 g (94% of theory) of the title compound in a purity of 90%.

Workup

  1. customthe organic phase is separated off
  2. extractionthe aqueous phase is extracted repeatedly with ethyl actate
  3. washThe combined organic phases are washed twice with water and once with saturated sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified on a silica gel column (mobile phase: cyclohexane→cyclohexane/ethyl acetate 10:1)

Sources & evidence

ORD record
ord-af04e7208a7f4ae9ab49990d13af7f1e
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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