Cesium carbonate → HCID 178500656, compound

HRID 2237618Notes

Reaction equation

HRID 2237618 reaction equation
[CH3:1][O:2][C:3](=[O:25])[CH2:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[CH:16]=[CH:15][C:14](OS(C(F)(F)F)(=O)=O)=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.[C:26]([Si:30]([CH3:36])([CH3:35])[O:31][CH2:32][CH2:33][NH2:34])([CH3:29])([CH3:28])[CH3:27].C(=O)([O-])[O-].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCCCCCC.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:25])[CH2:4][C@H:5]1[CH2:10][CH2:9][C@H:8]([C:11]2[CH:16]=[CH:15][C:14]([NH:34][CH2:33][CH2:32][O:31][Si:30]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:36])[CH3:35])=[CH:13][CH:12]=2)[CH2:7][CH2:6]1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 529218(2-Aminoethoxy)(tert-butyl)dimethylsilaneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 178500691HCID 178500691, compound2×

Product 1

HCID 178500656HCID 178500656, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent2×HCID 8900HeptaneSolvent

Procedure

Methyl[trans-4-[4-[[(trifluoromethyl)sulfonyl]oxy]phenyl]cyclohexyl]acetate, shown above, which is identified as Compound 55 in U.S. Pat. No. 7,244,727, issued Jul. 17, 2007, was prepared according to the method described therein. A mixture of methyl[trans-4-[4-[[(trifluoromethyl)-sulfonyl]oxy]phenyl]cyclohexyl]acetate (10.1 g, 26.6 mmol), 2-{[tert-butyl (dimethyl)silyl]oxy}ethanamine (5.59 g, 31.9 mmol), which can be prepared by various methods including those disclosed in Journal of the American Chemical Society, 129(37), 11408-11420; 2007, Organic Letters, 9(1), 101-104; 2007 or Bioorganic & Medicinal Chemistry, 13(11), 3821-3839; 2005, cesium carbonate (8.65 g, 26.6 mmol), palladium acetate (0.60 g, 2.66 mmol) and X-PHOS (1.27 g, 2.66 mmol) in toluene (53 mL) under nitrogen was heated in a sealed tube at 120° C. for 16 hours. The reaction was cooled, diluted into EtOAc, washed with water (2×), saturated aqueous brine, dried over sodium sulfate and concentrated to afford a dark oil. Chromatography (330 g Biotage Snap Cartridge® silica gel column, 0-15% EtOAc:heptane) afforded methyl(trans-4-{4-[(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-amino]phenyl}cyclohexyl)acetate as a light-yellow oil, 6.70 g. 1H NMR (400 MHz, CDCl3): δ 7.02, (d, 2H), 6.61 (d, 2H), 3.80 (m, 2H), 3.64 (s, 3H), 3.20 (m, 2H), 2.37 (m, 1H), 2.24 (m, 2H), 1.85 (m, 5H), 1.44 (m, 2H), 1.13 (m, 2H), 0.87 (s, 9H), 0.04 (s, 6H). m/z=406.4 (M+1).

Workup

  1. custom17, 2007, was prepared
  2. customcan be prepared by various methods
  3. temperatureThe reaction was cooled
  4. washwashed with water (2×), saturated aqueous brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto afford a dark oil

Sources & evidence

ORD record
ord-5951cd7cead646b5adf712607ea2ce79
Source dataset
uspto-grants-2010_05
Patent number
US07718645B2

Reaction notes

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