Water → 3-(5-Methoxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde

HRID 460299Notes

Reaction equation

HRID 460299 reaction equation
[H-].[Na+].[OH:3][CH2:4][C:5]1[CH:6]=[C:7]([C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=2[O:24][C:25]([F:28])([F:27])[F:26])[CH:19]=[O:20])[C:8]2[O:12][CH2:11][C:10]([CH3:14])([CH3:13])[C:9]=2[CH:15]=1.[CH3:29]I.O>O1CCCC1.C(OCC)(=O)C>[CH3:29][O:3][CH2:4][C:5]1[CH:6]=[C:7]([C:16]2[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=2[O:24][C:25]([F:28])([F:26])[F:27])[CH:19]=[O:20])[C:8]2[O:12][CH2:11][C:10]([CH3:13])([CH3:14])[C:9]=2[CH:15]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 184454093-(5-Hydroxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde

Product 1

HCID 184454133-(5-Methoxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehydeYield 39%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a cold solution (0° C.) of sodium hydride in tetrahydrofuran (4 mL), under an atmosphere of argon, was added 3-(5-hydroxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde (example 10c) (246 mg, 0.67 mmol) in tetrahydrofuran (6 mL). The mixture was stirred at 0° C. for 15 minutes, then the argon flow was stopped and methyl iodide was added. After 3 hours at room temperature, the mixture was diluted with ethyl acetate. Water was slowly added and the layers separated. The organic layer was further washed with water, brine, dried (MgSO4), filtered and evaporated. The residue was chromatographed on silica gel (20% ethyl acetate in hexane) to afford 99 mg of 3-(5-Methoxymethyl-3,3-dimethyl-2,3-dihydro-benzofuran-7-yl)-4-trifluoromethoxy-benzaldehyde. 39% yield. 1H-NMR (300 MHz, CDCl3): 1.39 (s, 6H), 2.11 (s, 3H), 4.27 (s, 2H), 5.09 (s, 2H), 7.17 (s, 2H), 7.49 (d, J=8.5 Hz, 1H), 7.93 (dd, J1=8.5 Hz, J2=2.1 Hz, 1H), 8.02 (d, J=2.1 Hz, 1H), 10.03 (s, 1H).

Workup

  1. waitAfter 3 hours at room temperature
  2. customthe layers separated
  3. washThe organic layer was further washed with water, brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was chromatographed on silica gel (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-ae5a09b0984d4da9aba629a683271bdb
Source dataset
uspto-grants-2007_03
Patent number
US07196108B2

Reaction notes

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