tert-Butanol → (2,6-Difluoro-3,5-dimethoxy-phenyl)-carbamic Acid Tert-Butyl Ester

HRID 459944Notes

Reaction equation

HRID 459944 reaction equation
[F:1][C:2]1[C:10]([O:11][CH3:12])=[CH:9][C:8]([O:13][CH3:14])=[C:7]([F:15])[C:3]=1C(O)=O.C([N:18]([CH2:21]C)CC)C.[C:23]([OH:27])([CH3:26])([CH3:25])[CH3:24].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:35])C=CC=CC=1>C1(C)C=CC=CC=1>[C:23]([O:27][C:21](=[O:35])[NH:18][C:3]1[C:7]([F:15])=[C:8]([O:13][CH3:14])[CH:9]=[C:10]([O:11][CH3:12])[C:2]=1[F:1])([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 184447022,6-Difluoro-3,5-dimethoxybenzoic acid

Product 1

HCID 86590945(2,6-Difluoro-3,5-dimethoxy-phenyl)-carbamic Acid Tert-Butyl EsterYield 71%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred mixture of 47.7 g (0.22 mol) of 2,6-difluoro-3,5-dimethoxy benzoic acid, 32 mL (0.22 mol) of triethylamine and 16.2 g (0.22 mol) of t-butanol in 500 mL of toluene, 48.2 mL (0.22 mol) of diphenylphosphoryl azide was added in one portion and the mixture was heated to 60° C.–70° C. After approximately 1 hour, the reaction was completed and the mixture was cooled down. The toluene was removed in vacuo. Then, ethyl acetate was added and the resulting solution was washed two times with saturated potassium hydrogen-phosphate solution, two times with saturated sodium bicarbonate solution, one time with brine, dried over sodium sulfate, filtered and evaporated. The crude product was purified by column chromatography: 1 kg of silica eluting with dichloromethane to give 45 g (71%) of the title compound.

Workup

  1. additionwas added in one portion
  2. temperaturethe mixture was heated to 60° C.–70° C
  3. temperaturethe mixture was cooled down
  4. customThe toluene was removed in vacuo
  5. additionThen, ethyl acetate was added
  6. washthe resulting solution was washed two times with saturated potassium hydrogen-phosphate solution, two times with saturated sodium bicarbonate solution, one time with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-13e8387af2ac4144bd81fb285a1d161d
Source dataset
uspto-grants-2007_03
Patent number
US07196090B2

Reaction notes

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