Cesium carbonate → HCID 57464789, compound

HRID 587648Notes

Reaction equation

HRID 587648 reaction equation
I[C:2]1[C:3]2[N:4]([C:9]([CH2:12][CH:13]3[CH2:15][CH2:14]3)=[N:10][N:11]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH:16]1([B-](F)(F)F)[CH2:18][CH2:17]1.[K+].C12(P(C34CC5CC(CC(C5)C3)C4)CCCC)CC3CC(CC(C3)C1)C2.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:16]1([C:2]2[C:3]3[N:4]([C:9]([CH2:12][CH:13]4[CH2:15][CH2:14]4)=[N:10][N:11]=3)[CH:5]=[CH:6][C:7]=2[Cl:8])[CH2:18][CH2:17]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 11371790Bis(adamantan-1-yl)(butyl)phosphane2×HCID 23697338Potassium cyclopropyltrifluoroborate3×HCID 57459624HCID 57459624, compound

Product 1

HCID 57464789HCID 57464789, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalyst2×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of D70 (0.6 g, 1.8 mmol) in toluene (14 ml) under a nitrogen atmosphere were added potassium cyclopropyltrifluoroborate (0.799 g, 5.4 mmol), bis(adamantan-1-yl)(butyl)phosphine (0.019 g, 0.054 mmol), palladium(II) acetate (8.15 mg, 0.036 mmol) and Cs2CO3 (1.758 g, 5.4 mmol). The reaction mixture was heated at 100° C. overnight. After cooling, additional potassium cyclopropyltrifluoroborate (0.7 g, 4.71 mmol), bis(adamantan-1-yl)(butyl)phosphine (0.019 g, 0.054 mmol) and palladium(II) acetate (8.15 mg, 0.036 mmol) were added to the reaction mixture, which was then heated at 100° C. for 48 h. After cooling, more potassium cyclopropyltrifluoroborate (0.35 g, 2.37 mmol) was added and heated at 100° C. for 3 days. After cooling, the reaction mixture was diluted with EtOAc and washed with water. The organic layer was separated and concentrated in vacuo. The residue was purified by column chromatography (silica gel; DCM/EtOAc from 100/0 to 60/40 as eluent). The desired fractions were collected and concentrated in vacuo to yield intermediate D82 (0.217 g, 48.7%) as a yellow solid.

Workup

  1. temperatureAfter cooling
  2. temperaturewas then heated at 100° C. for 48 h
  3. temperatureAfter cooling
  4. temperatureheated at 100° C. for 3 days
  5. temperatureAfter cooling
  6. washwashed with water
  7. customThe organic layer was separated
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (silica gel; DCM/EtOAc from 100/0 to 60/40 as eluent)
  10. customThe desired fractions were collected
  11. concentrationconcentrated in vacuo
  12. customto yield intermediate D82 (0.217 g, 48.7%) as a yellow solid

Sources & evidence

ORD record
ord-b3fc8a45a4034443aca54076fa2b245b
Source dataset
uspto-grants-2016_01
Patent number
US09226930B2

Reaction notes

Loading…