tert-Butanol → Tert-butyl [4-(4-benzyloxycarbonylamino-3-fluorophenoxy)pyridin-2-yl]carbamate

HRID 388491Notes

Reaction equation

HRID 388491 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:27]=[CH:26][C:15]([O:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19](C(O)=O)[CH:18]=2)=[CH:14][C:13]=1[F:28])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N:31]([CH2:34]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:43])C=CC=CC=1.C(OCC)(=O)C.[C:59]([OH:63])([CH3:62])([CH3:61])[CH3:60]>>[CH2:1]([O:8][C:9]([NH:11][C:12]1[CH:27]=[CH:26][C:15]([O:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH:31][C:34](=[O:43])[O:63][C:59]([CH3:62])([CH3:61])[CH3:60])[CH:18]=2)=[CH:14][C:13]=1[F:28])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 5

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 199401P,P-Diphenylphosphinic azideHCID 231530984-(4-Benzyloxycarbonylamino-3-fluorophenoxy)pyridine-2-carboxylic acid

Product 1

HCID 57677355Tert-butyl [4-(4-benzyloxycarbonylamino-3-fluorophenoxy)pyridin-2-yl]carbamateYield 65.5%

Procedure

To a suspension of 4-(4-benzyloxycarbonylamino-3-fluorophenoxy)pyridine-2-carboxylic acid (5.04 g) in tert-butanol (50 ml) was added triethylamine (4.6 ml) at room temperature, and the mixture was stirred. Diphenylphosphoryl azide (3.13 ml) was then added at room temperature and stirring was continued for 30 minutes at room temperature under a nitrogen atmosphere. Heated stirring was then carried out at 90° C. for 30 minutes and at 100° C. for 4 hours. The reaction mixture was cooled to room temperature. Ethyl acetate (25 ml) was added, and the reaction mixture was stirred for 30 minutes while cooling on ice. The precipitated crystals were collected by filtration and washed with diethyl ether. The crystals were then dried under aeration for 1 hour at room temperature to give the title compound as colorless crystals (3.92 g; 65.5%).

Workup

  1. stirringstirring
  2. temperatureHeated
  3. stirringstirring
  4. waitwas then carried out at 90° C. for 30 minutes and at 100° C. for 4 hours
  5. stirringthe reaction mixture was stirred for 30 minutes
  6. temperaturewhile cooling on ice
  7. filtrationThe precipitated crystals were collected by filtration
  8. washwashed with diethyl ether
  9. customThe crystals were then dried under aeration for 1 hour at room temperature

Sources & evidence

ORD record
ord-aa7cf6a37d46408aa7083f2cd16e19c1
Source dataset
uspto-grants-2013_02
Patent number
US08377938B2

Reaction notes

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