Methanol → 2-(4-(Benzyloxy)-3-chlorophenyl)acetonitrile

HRID 39130Notes

Reaction equation

HRID 39130 reaction equation
CC([O-])(C)C.[K+].CC1C=CC(S([CH2:17][N+:18]#[C-])(=O)=O)=CC=1.[CH2:20]([O:27][C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][C:29]=1[Cl:36])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CO>C1COCC1.O>[CH2:20]([O:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][C:17]#[N:18])=[CH:30][C:29]=1[Cl:36])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 161915Tosylmethyl isocyanideHCID 27354954-(Benzyloxy)-3-chlorobenzaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 671206692-(4-(Benzyloxy)-3-chlorophenyl)acetonitrileYield 34.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of t-BuOK (11.7 g, 96 mmol) in THF (200 mL) was added a solution of TosMIC (9.4 g, 48 mmol) in THF (100 mL) at −78° C. The mixture was stirred for 15 minutes, treated with a solution of 4-benzyloxy-3-chloro-benzaldehyde (7.5 g, 30 mmol) in THF (50 mL) dropwise, and continued to stir for 1.5 hours at −78° C. To the cooled reaction mixture was added methanol (30 mL). The mixture was heated at reflux for 30 minutes. Solvent of the reaction mixture was removed to give a crude product, which was dissolved in water (300 mL). The aqueous phase was extracted with EtOAc (3×100 mL). The combined organic layers were dried and evaporated under reduced pressure to give crude product, which was purified by column chromatography (petroleum ether/EtOAc 10:1) to afford 2-(4-(benzyloxy)-3-chlorophenyl)acetonitrile (2.7 g, 34%). 1H NMR (400 MHz, CDCl3) δ 7.52-7.32 (m, 6H), 7.15 (dd, J=2.4, 8.4 Hz, 1H), 6.95 (d, J=8.4 Hz, 1H), 5.26 (s, 2H), 3.73 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 154.0, 136.1, 129.9, 128.7, 128.7, 128.1, 127.2, 127.1, 127.1, 124.0, 123.0, 117.5, 114.4, 70.9, 22.5.

Workup

  1. stirringto stir for 1.5 hours at −78° C
  2. customTo the cooled reaction mixture
  3. temperatureThe mixture was heated
  4. temperatureat reflux for 30 minutes
  5. customSolvent of the reaction mixture was removed
  6. customto give a crude product, which
  7. extractionThe aqueous phase was extracted with EtOAc (3×100 mL)
  8. customThe combined organic layers were dried
  9. customevaporated under reduced pressure
  10. customto give crude product, which
  11. customwas purified by column chromatography (petroleum ether/EtOAc 10:1)

Sources & evidence

ORD record
ord-d3f685124b8a4dc0ac7691109e6358c6
Source dataset
uspto-grants-2013_09
Patent number
US08524767B2

Reaction notes

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