Methane, dichloromethoxy- → 6-Methoxy-1-methyl-1-trifluoromethylisochroman-7-carbaldehyde

HRID 1978900Notes

Reaction equation

HRID 1978900 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9]([CH3:17])([C:13]([F:16])([F:15])[F:14])[O:8][CH2:7][CH2:6]2.[CH3:18][O:19]C(Cl)Cl>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[CH:18]=[O:19])[C:9]([CH3:17])([C:13]([F:16])([F:14])[F:15])[O:8][CH2:7][CH2:6]2

Participants

5

Reactant 2

HCID 21004Methane, dichloromethoxy-HCID 102205196-Methoxy-1-methyl-1-trifluoromethylisochroman

Product 1

HCID 98169706-Methoxy-1-methyl-1-trifluoromethylisochroman-7-carbaldehydeYield 48.3%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 6-methoxy-1-methyl-1trifluoromethylisochroman (460 mg) in dry dichloromethane (5 ml) was added titanium(IV) chloride under nitrogen at −78° C. After 15 minutes, to the yellow solution was added a solution of dichloromethyl methyl ether in dry dichloromethane at the same temperature. The reaction mixture was stirred at −78° C. for one hour, poured onto ice water, and stirred at room temperature for 30 minutes. The aqueous layer was extracted with methylene chloride. The extracts were washed with brine, dried over magnesium sulfate, and concentrated to give a crude product. This was purified by silica-gel column chromatography eluted with a gradient of hexane and ethyl acetate (10:1, 8:1, 6:1) to give the title compound (179 mg, 48.3% from 1,1,1-Trifluoro-2-(4-methoxy-2-(2-(tetrahydropyran-2-yloxy)ethyl)phenyl)-propan-2-ol). 1H-NMR(CDCl3): 10.41 (s, 1H), 7.82 (s, 1H), 6.78 (s, 1H), 4.19-4.11 (m, 1H), 3.94 (s, 3H), 3.94-3.87 (m, 1H), 2.91 (t, J=4.4 Hz, 2H), 1.67 (s, 3H).

Workup

  1. additionpoured onto ice water
  2. stirringstirred at room temperature for 30 minutes
  3. extractionThe aqueous layer was extracted with methylene chloride
  4. washThe extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customto give a crude product
  8. customThis was purified by silica-gel column chromatography
  9. washeluted with a gradient of hexane and ethyl acetate (10:1, 8:1, 6:1)

Sources & evidence

ORD record
ord-35467beef0814428bec4ea2d7283c287
Source dataset
uspto-grants-2001_05
Patent number
US06239147B1

Reaction notes

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