4-Methyloxybenzyl chloride → Methyl (3,5-dibromo-4-fluorophenyl)(4-methoxybenzyl)carbamate

HRID 921745Notes

Reaction equation

HRID 921745 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11](=[O:14])[O:12][CH3:13])[CH:5]=[C:6]([Br:9])[C:7]=1[F:8].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([N:10]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=2)[C:11](=[O:14])[O:12][CH3:13])[CH:5]=[C:6]([Br:9])[C:7]=1[F:8]

Participants

5

Reactant 3

HCID 699934-Methyloxybenzyl chlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 86708627Methyl (3,5-dibromo-4-fluorophenyl)carbamate

Product 1

HCID 86708628Methyl (3,5-dibromo-4-fluorophenyl)(4-methoxybenzyl)carbamateYield 90.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of methyl (3,5-dibromo-4-fluorophenyl)carbamate (0.82 g, 2.508 mmol) in DMF (20 mL) was treated with sodium bis(trimethylsilyl)amide (3.01 mL, 3.01 mmol), stirred at room temperature for 30 minutes, then 1-(chloromethyl)-4-methoxybenzene (0.410 mL, 3.01 mmol) was added, stirred at 70° C. for two hours. The reaction mixture was partitioned between NH4Cl solution and EtOAc. The organic layer was washed with NaHCO3 solution (2×), then brine, then dried over MgSO4, filtered and evaporated to dryness to give 1.40 g colorless film, which was purified by column chromatography on silica (120 g silica, gradient from 100% hexanes to 20% EtOAc in hexanes) to give methyl (3,5-dibromo-4-fluorophenyl)(4-methoxybenzyl)carbamate (1.01 g)

Workup

  1. stirringstirred at 70° C. for two hours
  2. customThe reaction mixture was partitioned between NH4Cl solution and EtOAc
  3. washThe organic layer was washed with NaHCO3 solution (2×)
  4. dry with materialbrine, then dried over MgSO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customto give 1.40 g colorless film, which
  8. customwas purified by column chromatography on silica (120 g silica, gradient from 100% hexanes to 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c359985eb5e14b0b9dd1eeb4b0e6ccb2
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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