tert-Butanol → Tert-butyl (4-chloro-2,6-difluorophenyl)carbamate

HRID 634687Notes

Reaction equation

HRID 634687 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([F:11])[C:5](C(O)=O)=[C:4]([F:12])[CH:3]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:20])C=CC=CC=1.C([N:32]([CH2:35]C)CC)C.[C:37]([OH:41])([CH3:40])([CH3:39])[CH3:38]>>[C:37]([O:41][C:35]([NH:32][C:5]1[C:4]([F:12])=[CH:3][C:2]([Cl:1])=[CH:10][C:9]=1[F:11])=[O:20])([CH3:40])([CH3:39])[CH3:38]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 177506844-Chloro-2,6-difluorobenzoic acid

Product 1

HCID 21260314Tert-butyl (4-chloro-2,6-difluorophenyl)carbamateYield 25%

Procedure

4-Chloro-2,6-difluorobenzoic acid (500 mg, 2.6 mmol) was added to a solution of diphenylphosphoryl azide (737 mg, 3 mmol) in t-butanol (8 ml) followed by triethylamine (477 ml, 6 mmol) and the mixture heated at reflux for 2 hours. The reaction mixture was allowed to cool and the solvent removed by evaporation. The residue was dissolved in ethyl acetate, washed with water, dried (MgSO4) and purified by column chromatography eluting with increasingly polar mixtures of methylene chloride, hexane and methanol (/1/1/0 to 95/0/5) to give N-t-butoxycarbonyl-4-chloro-2,6-difluoroaniline (170 mg, 25%).

Workup

  1. temperaturethe mixture heated
  2. temperatureat reflux for 2 hours
  3. temperatureto cool
  4. customthe solvent removed by evaporation
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washwashed with water
  7. dry with materialdried (MgSO4)
  8. custompurified by column chromatography
  9. washeluting
  10. temperaturewith increasingly polar mixtures of methylene chloride, hexane and methanol (/1/1/0 to 95/0/5)

Sources & evidence

ORD record
ord-a45f85b71b2f406ebe44ab1a50d47d87
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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