Sodium Iodide → Tert-butyl(trans)-2-{4-[(4-cyanobenzyl)oxy]phenyl}cyclopropylcarbamate

HRID 1844244Notes

Reaction equation

HRID 1844244 reaction equation
Br[CH2:2][C:3]1[CH:10]=[CH:9][C:6]([C:7]#[N:8])=[CH:5][CH:4]=1.[OH:11][C:12]1[CH:17]=[CH:16][C:15]([C@@H:18]2[CH2:20][C@H:19]2[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:14][CH:13]=1.C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CC(C)=O>[C:7]([C:6]1[CH:9]=[CH:10][C:3]([CH2:2][O:11][C:12]2[CH:17]=[CH:16][C:15]([C@@H:18]3[CH2:20][C@H:19]3[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[CH:14][CH:13]=2)=[CH:4][CH:5]=1)#[N:8]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 869964-(Bromomethyl)benzonitrileHCID 86672576tert-Butyl N-[(1R,2S)-rel-2-(4-hydroxyphenyl)cyclopropyl]carbamate

Product 1

HCID 86672578Tert-butyl(trans)-2-{4-[(4-cyanobenzyl)oxy]phenyl}cyclopropylcarbamateYield 71.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

4-(bromomethyl)benzonitrile (0.47 g, 2.40 mmol) was added to a mixture of Intermediate J, tert-butyl(trans)-2-(4-hydroxyphenyl)cyclopropylcarbamate, (0.50 g, 2.00 mmol), K2CO3 (0.42 g, 3.00 mmol) and NaI (0.03 g, 0.20 mmol) in acetone (15 mL) and stirred at room temperature for 3 d. After removal of the solvent, the crude residue was dissolved in EtOAc (30 mL) and washed with brine (2×25 mL). The organic layer was dried over anhydrous Na2SO4 and filtered. After removal of the solvent, the residue was purified by column chromatography on silica gel (5%-50% EtOAc/Hexanes), affording 0.52 g of tert-butyl(trans)-2-{4-[(4-cyanobenzyl)oxy]phenyl}cyclopropylcarbamate [Rf=0.2 (30% EtOAc/Hexanes), pale yellow solid, 71% yield].

Workup

  1. customAfter removal of the solvent
  2. dissolutionthe crude residue was dissolved in EtOAc (30 mL)
  3. washwashed with brine (2×25 mL)
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customAfter removal of the solvent
  7. customthe residue was purified by column chromatography on silica gel (5%-50% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-8ac8e857a20741048ef653797243f3f1
Source dataset
uspto-grants-2015_02
Patent number
US08946296B2

Reaction notes

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