Methyl chloroformate → HCID 20658728, compound

HRID 1633701Notes

Reaction equation

HRID 1633701 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][CH:8]=1)[NH2:5].C([O-])(O)=O.[Na+].[CH3:14][O:15][C:16](Cl)=[O:17].[Br:19]N1C(=O)CCC1=O.FC(F)(F)S(O)(=O)=O>C(Cl)Cl>[CH3:14][O:15][C:16](=[O:17])[NH:5][C:4]1[CH:6]=[CH:7][C:8]([Br:19])=[C:2]([F:1])[CH:3]=1

Participants

7

Reactant 5

HCID 6586Methyl chloroformateHCID 97423-FluoroanilineHCID 62406Trifluoromethanesulfonic acidHCID 67184N-bromobutanimideHCID 516892Sodium Bicarbonate

Product 1

HCID 20658728HCID 20658728, compoundYield 56,152.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 33.3 g (0.3 mol) 3-fluoroaniline in 160 ml CH2Cl2 were added 450 ml of a 0.7 M aqueous NaHCO3-solution. The resulting mixture was treated dropwise with 34.6 ml (0.41 mol) methylchloroformate within a period of 20 min. After stirring overnight the layers were separated and the organic layer was washed with saturated aqueous NaCl and dried with MgSO4. After evaporation of ca.60% of the solvent, 600 ml of hexane were added, whereby (3-Fluoro-phenyl)-carbamic acid methyl ester precipitated as a colorless solid that was filtered off and dried i.v (41 g (81%)). The solid was dissolved in 600 ml acetonitrile and treated subsequently with 50 g (0.28 mmol) N-bromosuccinimide and 2.13 ml (0.024 mol) trifluormethane sulfonic acid. After stirring at room temperature during 12 hours ca 50% of the solvent were evaporated, the resulting mixture diluted with 1000 ml EtOAc, and washed subsequently with saturated aqueous NaHCO3 and saturated aqueous NaCl. Drying of the combined organic layers with MgSO4, evaporation of the solvent, and column chromatography on silica gel with hexane/EtOAc 8:1 and then 2:1 gave 39 g (64%) (4-Bromo-3-fluoro-phenyl)-carbamic acid methyl ester as a colorless solid, that was dissolved in 390 ml acetonitrile, treated subsequently with 39 g (0.172 mol) N-iodosuccinimide and 1.4 ml (0.016 mol) trifluormethanesulfonic acid at 0° C. and left to stirr at room temperature during 10 hours. Cooling the reaction mixture to 0° C. led to precipitation of (4-Bromo-5-fluoro-2-iodo-phenyl)-carbamic acid methyl ester as colorless crystals that were filtered off and dried (26.7g, 44%). Dilution of the filtrate with 600 ml hexane followed by subsequent washing with saturated aqueous NaHCO3 and 0.5M aqueous NaS2O3, drying of the organic layer with MgSO4, evaporation of the solvent, and recrystallization of the residue in acetonitrile gave an additional 6.3 g (12%) of (4-Bromo-5-fluoro-2-iodo-phenyl)-carbamic acid methyl ester (total: 33 g, 56%), MS: 373 (M, 1Br).

Workup

  1. customwere separated
  2. washthe organic layer was washed with saturated aqueous NaCl
  3. dry with materialdried with MgSO4
  4. customAfter evaporation of ca
  5. addition60% of the solvent, 600 ml of hexane were added
  6. customwhereby (3-Fluoro-phenyl)-carbamic acid methyl ester precipitated as a colorless solid
  7. filtrationthat was filtered off
  8. customdried i.v (41 g (81%))
  9. dissolutionThe solid was dissolved in 600 ml acetonitrile
  10. customwere evaporated
  11. additionthe resulting mixture diluted with 1000 ml EtOAc
  12. washwashed subsequently with saturated aqueous NaHCO3 and saturated aqueous NaCl
  13. dry with materialDrying of the combined organic layers with MgSO4, evaporation of the solvent, and column chromatography on silica gel with hexane/EtOAc 8:1

Sources & evidence

ORD record
ord-d31307e6dc914e638b6ed1a7eb66ae62
Source dataset
uspto-grants-2003_01
Patent number
US06503907B2

Reaction notes

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