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

HRID 410447노트

반응식

HRID 410447 반응식
[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

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 9811564Bis(dibenzylideneacetone)palladium촉매

반응 조건

온도
100 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-718235bfc410429db94554b2aaed3bec
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759366B2

반응 노트

불러오는 중…