Diethyl Ether → [4-(dimethoxymethyl)phenyl]methanol

HRID 1873055Notes

Reaction equation

HRID 1873055 reaction equation
[C:1]([C:4]1[CH:11]=[CH:10]C(C=O)=[CH:6][CH:5]=1)(O)=[O:2].[CH3:12][O:13][C:14]([O:17][CH3:18])([CH3:16])C.CC1C=CC(S(O)(=O)=O)=CC=1.O.[H-].[H-].[H-].[H-].[Li+].[Al+3].CCOCC>CO.C1COCC1>[CH3:18][O:17][CH:14]([O:13][CH3:12])[C:16]1[CH:10]=[CH:11][C:4]([CH2:1][OH:2])=[CH:5][CH:6]=1

Participants

8

Reactant 5

HCID 3283Diethyl EtherHCID 64952,2-DimethoxypropaneHCID 120884-Formylbenzoic acidHCID 521998p-Toluenesulfonic acid monohydrateHCID 21226445Aluminium lithium hydride

Product 1

HCID 3391102[4-(dimethoxymethyl)phenyl]methanol

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 4-carboxybenzaldehyde (7.51 g, 50 mmol) in dry MeOH (40 ml) was added 8 ml (65 mmol) of 2,2-dimethoxypropane and a catalytic amount of p-TsOH.H2O (190 mg, 1 mmol). The suspension cleared, then a colorless precipitate appeared (5 ml of dry MEOH added) and the thick suspension was stirred over night, before 100 mg of NaHCO5 were added and the mixture was concentrated in vacuo. The residue was tho roughly dried at high vacuum, dissolved in dry THF (50 ml) and added dropwise to an ice cooled slurry of LiAlH4 (1.71 g, 45 mmol) in 40 ml of dry THF. After the addition was complete (30 min), the cooling bath was removed and stirring was continued for 5 h, before the reaction mixture was treated with 1N HCl till Al-salts have precipitated (pH 9-10). The organic layer was decanted and the remaining salts were washed several times with Et2O, then treated with H2O/1N HCl and extracted several times with Et2O. All organic layers were combined, washed with brine, dried over MgSO4 and concentrated in vacuo. The crude product was chromatographed (500 g silica gel +0.5% Et3N, Hex/Et2O 2:3) to afford after crystallization from Hex/Et2O 5.66 g 31.1 mmol, 62%) of a colorless, fluffy powder (m.p. 43.5-45° C.). 1H NMR (400 MHz, CDCl3) d 7.44 (d, J=8.1, 2 H), 7.36 (d, J=m8.1, 2 H), 5.39 (s, 1 H), 4.69 (d, J=5.9, 2 H), 3.32 (s, 6 H), 1.92 (t, J=5.9, 1 H); 13C NMR (100 MHz, CDCl3) d 141.10, 137.31, 126.89, 126.73, 102.86, 64.91, 52.61; HRMS calcd for C10H14O3Na =(M+Na)+ 205.0841, found 205.0847.

Workup

  1. addition(5 ml of dry MEOH added)
  2. additionwere added
  3. concentrationthe mixture was concentrated in vacuo
  4. customThe residue was tho roughly dried at high vacuum
  5. dissolutiondissolved in dry THF (50 ml)
  6. additionAfter the addition
  7. custom(30 min)
  8. customthe cooling bath was removed
  9. additionwas treated with 1N HCl till Al-salts
  10. customhave precipitated (pH 9-10)
  11. customThe organic layer was decanted
  12. washthe remaining salts were washed several times with Et2O
  13. additiontreated with H2O/1N HCl
  14. extractionextracted several times with Et2O
  15. washwashed with brine
  16. dry with materialdried over MgSO4
  17. concentrationconcentrated in vacuo
  18. customThe crude product was chromatographed (500 g silica gel +0.5% Et3N, Hex/Et2O 2:3)
  19. customto afford

Sources & evidence

ORD record
ord-73bb4ba21ba9450d90ff67c998896837
Source dataset
uspto-grants-2000_08
Patent number
US06111084

Reaction notes

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