tert-Butanol → 3-Chloro-2,6-difluoroaniline

HRID 2367154Notes

Reaction equation

HRID 2367154 reaction equation
[Cl:1][C:2]1[C:3]([F:12])=[C:4]([C:8]([F:11])=[CH:9][CH:10]=1)C(O)=O.C([N:15]([CH2:18]C)CC)C.C1(P([N:34]=[N+]=[N-])(C2C=CC=CC=2)=[O:27])C=CC=CC=1.[CH3:37][C:38]([OH:41])([CH3:40])[CH3:39]>CN(C=O)C>[Cl:1][C:2]1[C:3]([F:12])=[C:4]([NH:15][C:18](=[O:27])[O:41][C:38]([CH3:40])([CH3:39])[CH3:37])[C:8]([F:11])=[CH:9][CH:10]=1.[Cl:1][C:2]1[C:3]([F:12])=[C:4]([C:8]([F:11])=[CH:9][CH:10]=1)[NH2:34]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 27735343-Chloro-2,6-difluorobenzoic acid

Product 2

HCID 177507453-Chloro-2,6-difluoroanilineYield 20%HCID 86083514tert-Butyl (3-chloro-2,6-difluorophenyl)carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-chloro-2,6-difluorobenzoic acid (500 mg, 2.6 mmol) in DMF (7.5 mL) was added triethylamine (362 μL, 2.6 mmol) and diphenylphosphoryl azide (560 μL, 2.6 mmol). After the mixture was stirred at rt for 1.25 h, 2-methyl-2-propanol (2.5 mL) was added, and the mixture was heated to 90° C. for 2 h. Upon cooling to rt, the solvents were removed in vacuo. The residue was partitioned between water and ethyl acetate. The aqueous was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by flash chromatography (80% hexanes: 20% ethyl acetate) yielding 1,1-dimethylethyl (3-chloro-2,6-difluorophenyl)carbamate as a white waxy solid (contaminated with approximately 20% of the aniline). 1H NMR (400 MHz, CDCl3): 7.24 (m, 1H), 6.91 (m, 1H), 5.99 (br s, 1H), 1.51 (s, 9H); GCMS for C11H12ClF2NO2: 263 (M+).

Workup

  1. temperaturethe mixture was heated to 90° C. for 2 h
  2. temperatureUpon cooling to rt
  3. customthe solvents were removed in vacuo
  4. customThe residue was partitioned between water and ethyl acetate
  5. extractionThe aqueous was extracted with ethyl acetate
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography (80% hexanes: 20% ethyl acetate)

Sources & evidence

ORD record
ord-de480e3dd4c440b69a7f8be74adf7047
Source dataset
uspto-grants-2014_04
Patent number
US08697737B2

Reaction notes

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