Potassium Carbonate → tert-Butyl 4-(2,6-dicarbamoylpyridin-4-yloxy)-3-fluorophenylcarbamate

HRID 1670290Notes

Reaction equation

HRID 1670290 reaction equation
[C:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([F:16])[CH:10]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CC([O-])(C)C.[K+].Cl[C:24]1[CH:29]=[C:28]([C:30]([NH2:32])=[O:31])[N:27]=[C:26]([C:33]([NH2:35])=[O:34])[CH:25]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:30]([C:28]1[CH:29]=[C:24]([O:15][C:12]2[CH:13]=[CH:14][C:9]([NH:8][C:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[CH:10][C:11]=2[F:16])[CH:25]=[C:26]([C:33](=[O:34])[NH2:35])[N:27]=1)(=[O:31])[NH2:32]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 11708410tert-Butyl (3-Fluoro-4-hydroxyphenyl)carbamateHCID 199059102,6-Pyridinedicarboxamide, 4-chloro-HCID 23665647Potassium tert-butoxide

Product 1

HCID 59852866tert-Butyl 4-(2,6-dicarbamoylpyridin-4-yloxy)-3-fluorophenylcarbamateYield 44%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of N-Boc-4-amino-2-fluorophenol (228 mg, 1.0 mmol) in DMF (2 mL) was treated with t-BuOK (124 mg, 1.1 mmol) and the mixture stirred at room temperature for 2 h. The mixture was treated with 4-chloropyridine-2,6-dicarboxamide (200 mg, 1.0 mmol) and K2CO3 (35 mg, 0.5 mmol) and heated at 80° C. for 1.5 h. The mixture was concentrated in vacuo, treated with EtOAc (10 mL) and H2O (10 mL) and filtered to remove the insoluble material. The EtOAc phase was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the residue by flash column chromatography on SiO2 eluting with 30-100% EtOAc/hexanes gave the title compound (170 mg, 44%) as a white solid containing 10% of the starting chloropyridine. 1H NMR (DMSO-d6) δ 9.77 (s, 1H), 8.86 (s, 2H), 7.87 (s, 1H), 7.63 (d, 1H, J=12.1 Hz), 7.55 (s, 2H), 7.38-7.31 (m, 2H), 1.48 (s, 9H).

Workup

  1. temperatureheated at 80° C. for 1.5 h
  2. concentrationThe mixture was concentrated in vacuo
  3. additiontreated with EtOAc (10 mL) and H2O (10 mL)
  4. filtrationfiltered
  5. customto remove the insoluble material
  6. washThe EtOAc phase was washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by flash column chromatography on SiO2 eluting with 30-100% EtOAc/hexanes

Sources & evidence

ORD record
ord-a9940d0b122843b4861d0071c1baade5
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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