Water → 4-({4-[(trans)-2-Aminocyclopropyl]phenoxy}methyl)benzonitrile

HRID 1844245Notes

Reaction equation

HRID 1844245 reaction equation
[C:1]([C:3]1[CH:27]=[CH:26][C:6]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[CH2:17][C@H:16]3[NH:18]C(=O)OC(C)(C)C)=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)#[N:2].O.[OH-].[Na+]>O1CCOCC1.OS(O)(=O)=O>[NH2:18][C@@H:16]1[CH2:17][C@H:15]1[C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:27][CH:26]=2)=[CH:10][CH:11]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 86672578Tert-butyl(trans)-2-{4-[(4-cyanobenzyl)oxy]phenyl}cyclopropylcarbamate

Product 1

HCID 671146174-({4-[(trans)-2-Aminocyclopropyl]phenoxy}methyl)benzonitrileYield 85%

Reagents, catalysts & solvents 1

HCID 19613996Dioxane sulfuric acidSolvent

Procedure

tert-butyl(trans)-2-{4-[(4-cyanobenzyl)oxy]phenyl}cyclopropylcarbamate (0.31 g, 0.85 mmol) was dissolved in a mixture of 1,4-dioxane/H2SO4 (15 mL, 10:1, v/v) and stirred at room temperature for 45 min. The reaction mixture was poured into water (15 mL), basified by addition of 15 mL of aqueous NaOH (10%) and extracted with EtOAc (2×15 mL); the organic layers were washed with brine (20 mL), dried over anhydrous Na2SO4 and filtered. After removal of the solvent, the crude residue was purified by column chromatography on silica gel (0%-3% MeOH/CH2Cl2) to afford 0.19 g of 4-({4-[(trans)-2-aminocyclopropyl]phenoxy}methyl)benzonitrile [Rf=0.2 (5% MeOH/CH2Cl2), beige solid, 85% yield].

Workup

  1. extractionextracted with EtOAc (2×15 mL)
  2. washthe organic layers were washed with brine (20 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. customAfter removal of the solvent
  6. customthe crude residue was purified by column chromatography on silica gel (0%-3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-31ff562f19c14c0e9db2c4b8e40b1d5d
Source dataset
uspto-grants-2015_02
Patent number
US08946296B2

Reaction notes

Loading…