Ethyl Acetate → Tert-butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)(4-methoxybenzyl)carbamate

HRID 921771Notes

Reaction equation

HRID 921771 reaction equation
[Br:1][C:2]1[C:3]([Cl:20])=[C:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:5]=[C:6]([O:8][CH:9]([F:11])[F:10])[CH:7]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:31][O:32][C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Cl)=[CH:35][CH:34]=1.CCOC(C)=O>CN(C=O)C>[Br:1][C:2]1[C:3]([Cl:20])=[C:4]([N:12]([CH2:37][C:36]2[CH:39]=[CH:40][C:33]([O:32][CH3:31])=[CH:34][CH:35]=2)[C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:17])[CH3:18])[CH:5]=[C:6]([O:8][CH:9]([F:11])[F:10])[CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 699934-Methyloxybenzyl chlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 131734933Tert-butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)carbamate

Product 1

HCID 117925637Tert-butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)(4-methoxybenzyl)carbamateYield 72.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

tert-Butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)carbamate (2.78 g, 7.46 mmol) was dissolved in DMF (37.3 ml) at room temperature. NaHMDS (8.95 ml, 8.95 mmol) was added drop wise and the reaction mixture was stirred for 30 min before the addition of 4-methoxybenzyl chloride (1.321 ml, 9.70 mmol). The reaction was allowed to stir overnight. EtOAc (250 mL) was added and the organic layer was washed with 10% LiCl solution (2×, dried over Na2SO4 and concentrated. Column chromatography (120 g SiO2, 0 to 10% EtOAc-hexane gradient elution) afforded tert-butyl (3-bromo-2-chloro-5-(difluoromethoxy)phenyl)(4-methoxybenzyl)carbamate as a clear oil (2.68 g)

Workup

  1. washthe organic layer was washed with 10% LiCl solution (2×
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. washColumn chromatography (120 g SiO2, 0 to 10% EtOAc-hexane gradient elution)

Sources & evidence

ORD record
ord-d5b1e9ad42934526a9495766bb336644
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…