Methane, dichloromethoxy- → 5-Hydroxy-7-isopropyl-4-oxo-3,4-dihydrospiro[chromen-2,1'-cyclobutane]-6-carbaldehyde

HRID 1516715Notes

Reaction equation

HRID 1516715 reaction equation
[OH:1][C:2]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[CH:12]=[C:11]2[C:3]=1[C:4](=[O:18])[CH2:5][C:6]1([O:10]2)[CH2:9][CH2:8][CH2:7]1.[CH3:19][O:20]C(Cl)Cl>[Ti](Cl)(Cl)(Cl)Cl.ClCCl>[OH:1][C:2]1[C:14]([CH:19]=[O:20])=[C:13]([CH:15]([CH3:16])[CH3:17])[CH:12]=[C:11]2[C:3]=1[C:4](=[O:18])[CH2:5][C:6]1([O:10]2)[CH2:7][CH2:8][CH2:9]1

Participants

5

Reactant 2

HCID 21004Methane, dichloromethoxy-HCID 58002934HCID 58002934, compound

Product 1

HCID 580029765-Hydroxy-7-isopropyl-4-oxo-3,4-dihydrospiro[chromen-2,1'-cyclobutane]-6-carbaldehyde

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
-70 °C

Procedure

Under argon, 9.60 g (39 mmol) of 5-hydroxy-7-isopropylspiro[chromen-2,1′-cyclobutan]-4(3H)-one (Example 46A) are dissolved in 400 ml of abs. dichloromethane and cooled to −70° C. At this temperature, 97.44 ml (97.44 mmol) of titanium(IV) chloride (1 M solution in dichloromethane) are added dropwise such that the temperature does not exceed −65° C. The mixture is stirred briefly at −70° C., 3.88 ml (42.87 mmol) of dichloromethyl methyl ether are then added and the mixture is subsequently warmed to 0° C. After 3 hours at this temperature, the reaction mixture is added carefully to ice-water and extracted four times with dichloromethane. The combined organic phases are washed three times with saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated to dryness. The crude product obtained is adsorbed on silica gel and purified on a silica gel column (mobile phase: cyclohexane→cyclohexane/ethyl acetate 30:1). This gives 8.1 g (76% of theory) of the title compound in a purity of 77%.

Workup

  1. customdoes not exceed −65° C
  2. temperaturethe mixture is subsequently warmed to 0° C
  3. extractionextracted four times with dichloromethane
  4. washThe combined organic phases are washed three times with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-6585295027b24077a02f7e0b265ae83c
Source dataset
uspto-grants-2012_07
Patent number
US08227511B2

Reaction notes

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