Cesium carbonate → methyl(1S,4R)-4-{5-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-nitrophenyl]-1,3-thiazol-2-yl}-4-hydroxy-2,2-dimethylcyclohexanecarboxylate

HRID 1039947노트

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HRID 1039947 반응식
[C:1]([Si:5]([CH3:27])([CH3:26])[O:6][CH2:7][C:8]1[CH:13]=[C:12](B2OC(C)(C)C(C)(C)O2)[CH:11]=[C:10]([N+:23]([O-:25])=[O:24])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].Br[C:29]1[S:33][C:32]([C@@:34]2([OH:46])[CH2:39][CH2:38][C@H:37]([C:40]([O:42][CH3:43])=[O:41])[C:36]([CH3:45])([CH3:44])[CH2:35]2)=[N:31][CH:30]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>O1CCOCC1.O.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]>[Si:5]([O:6][CH2:7][C:8]1[CH:13]=[C:12]([C:29]2[S:33][C:32]([C@@:34]3([OH:46])[CH2:39][CH2:38][C@H:37]([C:40]([O:42][CH3:43])=[O:41])[C:36]([CH3:44])([CH3:45])[CH2:35]3)=[N:31][CH:30]=2)[CH:11]=[C:10]([N+:23]([O-:25])=[O:24])[CH:9]=1)([C:1]([CH3:2])([CH3:3])[CH3:4])([CH3:26])[CH3:27]

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 58456350(1S,4R)-4-(5-Bromo-thiazol-2-yl)-4-hydroxy-2,2-dimethyl-cyclohexanecarboxylic acid methyl esterHCID 67433819Tert-butyl(dimethyl){[3-nitro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]oxy}silane

생성물 1

HCID 67432153methyl(1S,4R)-4-{5-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-nitrophenyl]-1,3-thiazol-2-yl}-4-hydroxy-2,2-dimethylcyclohexanecarboxylate수율 54,305.602%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a stirring solution of the product of Step 2 (7.91 g, 20.1 mmol) in dioxane (30 mL) and water (4 mL) was added methyl(1S,4R)-4-(5-bromo-1,3-thiazol-2-yl)-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (5 g, 14.4 mmol) and cesium carbonate (14 g, 43.1 mmol). The solution was deoxygenated, then tris(dibenzylideneacetone)dipalladium(0) (0.66 g, 0.72 mmol) and 2-(dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (0.68 g, 1.44 mmol) were added and the mixture was stirred at 100° C. for 15 h. The mixture was cooled to room temperature and quenched with 1:1 saturated aqueous sodium bicarbonate:brine. The mixture was extracted with ethyl acetate, and the organic layer was dried over sodium sulfate, filtered, and concentrated. Purification by flash chromatography on silica gel (0-50% ethyl acetate in hexanes) afforded methyl(1S,4R)-4-{5-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-nitrophenyl]-1,3-thiazol-2-yl}-4-hydroxy-2,2-dimethylcyclohexanecarboxylate (4.4 g, 7.82 mol, 54% yield) as an orange oil. MS ESI: [M+H]+ m/z 535.2.

후처리

  1. customThe solution was deoxygenated
  2. temperatureThe mixture was cooled to room temperature
  3. customquenched with 1:1 saturated aqueous sodium bicarbonate
  4. extractionThe mixture was extracted with ethyl acetate
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash chromatography on silica gel (0-50% ethyl acetate in hexanes)

출처 및 근거

ORD 기록
ord-a6eff2aaee2546b0b2da494a56ab7d84
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551984B2

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