Cesium carbonate → tert-Butyl 6-(4-nitrophenoxy)pyrimidin-4-ylcarbamate

HRID 2069145Notes

Reaction equation

HRID 2069145 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][CH:10]=2)[N:5]=[CH:4][N:3]=1.[C:18](=[O:25])([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[NH2:19].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N+:15]([C:12]1[CH:13]=[CH:14][C:9]([O:8][C:6]2[N:5]=[CH:4][N:3]=[C:2]([NH:19][C:18](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:7]=2)=[CH:10][CH:11]=1)([O-:17])=[O:16]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 77922tert-Butyl carbamateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 143638504-Chloro-6-(4-nitrophenoxy)pyrimidine

Product 1

HCID 70881437tert-Butyl 6-(4-nitrophenoxy)pyrimidin-4-ylcarbamateYield 61.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

A degassed mixture of 4-chloro-6-(4-nitrophenoxy)pyrimidine (WO 2006072589) (1.50 g, 5.96 mmol), tert-butyl carbamate (2.10 g, 17.9 mmol), cesium carbonate (2.91 g, 8.94 mmol), Pd2dba3 (0.218 g, 0.238 mmol) and Xantphos (0.276 g, 0.477 mmol) in DMF was heated at reflux for 1 hr and then maintained at RT for 16 hr. The resulting mixture was partitioned between water (100 mL) and EtOAc (100 mL) and the organic layer was separated and washed with water (2×50 mL) and brine (50 mL) and then dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, EtOAc in DCM, 0-100%, gradient elution) to afford the title compound as a beige solid (1.22 g, 85% purity, 52%); Rt 4.90 min (Method 1 basic); m/z 331 (M−H)− (ES−).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 hr
  3. customThe resulting mixture was partitioned between water (100 mL) and EtOAc (100 mL)
  4. customthe organic layer was separated
  5. washwashed with water (2×50 mL) and brine (50 mL)
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by flash column chromatography (SiO2, EtOAc in DCM, 0-100%, gradient elution)

Sources & evidence

ORD record
ord-74ec0c6d4236469d9add7b9e0abf2b74
Source dataset
uspto-grants-2012_10
Patent number
US08299074B2

Reaction notes

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