Cesium carbonate → 8-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decan-8-ol

HRID 410447Notes

Reaction equation

HRID 410447 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:34])[CH2:33][CH2:32][C:27]3([O:31][CH2:30][CH2:29][O:28]3)[CH2:26][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:34])[CH2:33][CH2:32][C:27]4([O:31][CH2:30][CH2:29][O:28]4)[CH2:26][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 672560328-(5-Bromo-1,3-thiazol-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol

Product 1

HCID 584562088-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decan-8-olYield 65%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (2.00 g, 8.58 mmol), the product of Step 2 (2.75 g, 8.58 mmol), X-Phos (0.409 g, 0.858 mmol), cesium carbonate (8.39 g, 25.7 mmol), and Pd2(dba)3 (0.393 g, 0.429 mmol) were placed in a flask flushed with Argon. Degassed Dioxane (30 ml) and Water (3 mL) were added and the reaction was heated to 100° C. for 40 h. The reaction was then cooled to room temperature, quenched with saturated aqueous sodium bicarbonate and extracted with EtOAc (3×). The combined organics were dried over Na2SO4 and concentrated in vacuo. Purification via flash chromatography (40%-100% EtOAc:hexanes) afforded 8-[5-(3-amino-5-methylphenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decan-8-ol (1.93 g, 65%) as a brown foam. MS EST: [M+H]+ m/z 347.

Workup

  1. customflushed with Argon
  2. additionDegassed Dioxane (30 ml) and Water (3 mL) were added
  3. temperatureThe reaction was then cooled to room temperature
  4. customquenched with saturated aqueous sodium bicarbonate
  5. extractionextracted with EtOAc (3×)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customPurification via flash chromatography (40%-100% EtOAc:hexanes)

Sources & evidence

ORD record
ord-718235bfc410429db94554b2aaed3bec
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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