Methanol → 2-Methoxy-3-(phenylmethoxy)benzeneacetonitrile

HRID 523990Notes

Reaction equation

HRID 523990 reaction equation
CC(C)([O-])C.[K+].C1(C)C=CC(S([CH2:16][N+:17]#[C-])(=O)=O)=CC=1.[CH2:20]([O:27][C:28]1[C:29]([O:36][CH3:37])=[C:30]([CH:33]=[CH:34][CH:35]=1)[CH:31]=O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CO>COCCOC.O>[CH2:20]([O:27][C:28]1[C:29]([O:36][CH3:37])=[C:30]([CH2:31][C:16]#[N:17])[CH:33]=[CH:34][CH:35]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 161915Tosylmethyl isocyanideHCID 154443393-(Benzyloxy)-2-methoxybenzaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 1173860082-Methoxy-3-(phenylmethoxy)benzeneacetonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
-50 °C

Procedure

9.3 g (83 mmol) Potassium tert-butoxide in 30 mL 1,2-dimethoxyethane are cooled to −30° C. 9.1 g (45 mmol) toluene-4-sulfonylmethylisocyanide in 30 mL 1,2-dimethoxyethan are added slowly and the resulting mixture is cooled to −50° C. A mixture of 10.0 g (41.3 mmol) 3-benzyloxy-2-methoxy-benzaldehyde (see CN 102451178) in 80 mL 1,2-dimethoxyethane are added within 30 min and stirred for 2 h at −50° C. After that time 60 mL MeOH are added and stirred for 2 h under reflux. The mixture is cooled to r.t., diluted with water and extracted with DCM. The organic layer is dried over MgSO4, filtered and the solvent is removed in vacuo. The residue is purified by column chromatography (silica gel; cyclohexane/EtOAc 4:1) to yield the desired product.

Workup

  1. additionare added within 30 min
  2. stirringstirred for 2 h
  3. temperatureunder reflux
  4. temperatureThe mixture is cooled to r.t.
  5. extractionextracted with DCM
  6. dry with materialThe organic layer is dried over MgSO4
  7. filtrationfiltered
  8. customthe solvent is removed in vacuo
  9. customThe residue is purified by column chromatography (silica gel; cyclohexane/EtOAc 4:1)

Sources & evidence

ORD record
ord-bd82f500d5594054bcd8ec3092b1a60b
Source dataset
uspto-grants-2016_05
Patent number
US09340510B2

Reaction notes

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