Cesium carbonate → HCID 67248215, compound

HRID 410443Notes

Reaction equation

HRID 410443 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:8]=1)[NH2:5].Br[C:19]1[S:23][C:22]([C:24]2([OH:36])[CH2:29][CH2:28][CH:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:26]([CH3:35])[CH2:25]2)=[N:21][CH:20]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[NH2:5][C:4]1[CH:6]=[C:7]([C:19]2[S:23][C:22]([C:24]3([OH:36])[CH2:29][CH2:28][CH:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:26]([CH3:35])[CH2:25]3)=[N:21][CH:20]=2)[CH:8]=[C:2]([CH3:1])[CH:3]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 672361713-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 67247723HCID 67247723, compound

Product 1

HCID 67248215HCID 67248215, compoundYield 83.5%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

To a round bottom flask containing 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (402 mg, 1.7 mmol), ethyl 4-(5-bromo-1,3-thiazol-2-yl)-4-hydroxy-2-methylcyclohexanecarboxylate (400 mg, 1.1 mmol), Pd2(dba)3 (105 mg, 0.11 mmol), X-phos (55 mg, 0.11 mmol) and Cs2CO3 (1.12 g, 3.45 mmol) was added 4.3 mL of degassed 10:1 1,4 dioxane/H2O. The reaction was heated to 100° C. for 16 h, then cooled and partitioned between EtOAc (50 mL) and saturated aqueous sodium bicarbonate (50 mL). The layers were separated and the aqueous phase was extracted once with EtOAc (50 mL). The combined organic phases were washed with brine (50 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. Purification of the resulting residue on silica furnished ethyl 4-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-4-hydroxy-2-methylcyclohexanecarboxylate (344 mg, 80%) as a colorless foam. MS ESI: [M+H]+ m/z 375.2.

Workup

  1. additionwas added 4.3 mL
  2. customof degassed 10:1 1,4 dioxane/H2O
  3. temperaturecooled
  4. custompartitioned between EtOAc (50 mL) and saturated aqueous sodium bicarbonate (50 mL)
  5. customThe layers were separated
  6. extractionthe aqueous phase was extracted once with EtOAc (50 mL)
  7. washThe combined organic phases were washed with brine (50 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customPurification of the resulting residue on silica

Sources & evidence

ORD record
ord-558c323d65264441827e5601a8db881f
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

Loading…