Water → HCID 22645392, compound

HRID 2414276Notes

Reaction equation

HRID 2414276 reaction equation
[CH2:1]([N:7]1[CH2:12][CH2:11][C:10]([CH3:27])([C:13]2[CH:18]=[CH:17][CH:16]=[C:15](OS(C(F)(F)F)(=O)=O)[CH:14]=2)[CH:9]([CH3:28])[CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].C(NC(C)C)(C)C.[CH3:36][Si:37]([C:40]#[CH:41])([CH3:39])[CH3:38].O>O1CCCC1.[Cu]I.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].ClCCl>[NH3:7].[CH2:1]([N:7]1[CH2:12][CH2:11][C:10]([CH3:27])([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:41]#[C:40][Si:37]([CH3:39])([CH3:38])[CH3:36])[CH:14]=2)[CH:9]([CH3:28])[CH2:8]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]

Participants

11

Reactant 4

HCID 962WaterHCID 7912DiisopropylamineHCID 66111TrimethylsilylacetyleneHCID 22645393HCID 22645393, compound

Product 2

HCID 222AmmoniaHCID 22645392HCID 22645392, compoundYield 97.8%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-hexyl-3,4-dimethyl-4-(3-trifluoromethanesulfonyloxyphenyl)piperidine (Preparation 1, 350 mg, 0.83 mmol) in tetrahydrofuran (12 mL) was added diisopropylamine (4 mL) and trimethylsilylethyne (4.5 g, 46 mmol) and the mixture was de-oxygenated by evacuating and flushing with nitrogen five times. Copper(I) iodide (6.2 mg 0.033 mmol), and then catalytic quantities of palladium(II) acetate and 1,1 ′-bis(diphenylphosphino)ferrocene were added. The reaction mixture was heated to reflux under nitrogen for 8 hours, before being allowed to cool to room temperature. Water (10 mL) and dichloromethane (10 mL) were added, the phases separated and the aqueous layer further extracted with dichloromethane (2×10 mL). The combined organics were then dried (Na2SO4) and the solvent removed in vacuo. The residual brown oil was purified by column chromatography on silica gel (25 g) eluted with a gradient of ethyl acetate:hexane:0.880 ammonia (20:79:1 to 50:49:1) to give the title compound as an oil (150 mg).

Workup

  1. customby evacuating
  2. customflushing with nitrogen five times
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux under nitrogen for 8 hours
  5. customthe phases separated
  6. extractionthe aqueous layer further extracted with dichloromethane (2×10 mL)
  7. dry with materialThe combined organics were then dried (Na2SO4)
  8. customthe solvent removed in vacuo
  9. customThe residual brown oil was purified by column chromatography on silica gel (25 g)
  10. washeluted with a gradient of ethyl acetate

Sources & evidence

ORD record
ord-3014fc02179b48f3b4c10646f8eb5a17
Source dataset
uspto-grants-2004_11
Patent number
US06812236B2

Reaction notes

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