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 410456Notes

Reaction equation

HRID 410456 reaction equation
[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]

Participants

8

Reactant 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

Product 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-dimethylcyclohexanecarboxylateYield 54,305.602%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-dce89a233f8643d48b7926a618b3a8a7
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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