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 410456ノート

反応式

HRID 410456 の反応式
[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]

参加物

8

反応物 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

生成物 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-dimethylcyclohexanecarboxylate収率 54,305.602%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-dce89a233f8643d48b7926a618b3a8a7
出典データセット
uspto-grants-2014_06
特許番号
US08759366B2

反応ノート

読み込み中…