Methyl iodide → 2-Methoxy-4-(2-tetrahydropyranyl)oxy-6-methylbenzaldehyde

HRID 1798141Notes

Reaction equation

HRID 1798141 reaction equation
[OH:1][C:2]1[CH:9]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:7]=[C:6]([CH3:17])[C:3]=1[CH:4]=[O:5].[H-].[Na+].[CH3:20]I>CN(C=O)C>[CH3:20][O:1][C:2]1[CH:9]=[C:8]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:7]=[C:6]([CH3:17])[C:3]=1[CH:4]=[O:5]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 10823699HCID 10823699, compound

Product 1

HCID 107531782-Methoxy-4-(2-tetrahydropyranyl)oxy-6-methylbenzaldehyde

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

An ice-cold yellow solution of 2-hydroxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde (7.60 g, 32.17 mmol) in DMF (150 mL), was treated with NaH (0.93 g, 38.63 mmol) in portions over 30 min. The suspension was stirred for 15 min, then methyl iodide (3.0 mL, 48.09 mmol) was added dropwise. The mixture was warmed to rt, stirred for 1 h, then quenched with water and extracted with EtOAc. The extracts were washed with brine, dried (Na2SO4), filtered and concentrated to a yellow liquid. The crude product of 2-methoxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ 10.49 (s, 1H), 6.50 (s, 1H), 6.49 (s, 1H), 5.54-5.52 (m, 1H), 3.87 (s, 1H), 3.88-3.80 (m, 1H), 3.67-3.61 (m, 1H), 2.57 (s, 3H), 2.10-1.95 (m, 1H), 1.95-1.82 (m, 2H), 1.80-1.58 (m, 3H).

Workup

  1. stirringstirred for 1 h
  2. customquenched with water
  3. extractionextracted with EtOAc
  4. washThe extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated to a yellow liquid
  8. customThe crude product of 2-methoxy-6-methyl-4-(tetrahydro-pyran-2-yloxy)-benzaldehyde was used in the next step without further purification

Sources & evidence

ORD record
ord-b3021de16a9b4edfafcdb208e452ddda
Source dataset
uspto-grants-2013_01
Patent number
US08343944B2

Reaction notes

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