Sodium Carbonate → 4-Dimethylamino-4-(3-fluorophenyl)-1-[3-(2-(triethylsilyl)-1h-indol-3-yl)propyl]cyclohexanol

HRID 2064528Notes

Reaction equation

HRID 2064528 reaction equation
[CH3:1][N:2]([CH3:29])[C:3]1([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=2)[CH2:8][CH2:7][C:6]([CH2:10][CH2:11][CH2:12][C:13]#[C:14][Si:15]([CH2:20][CH3:21])([CH2:18][CH3:19])[CH2:16][CH3:17])([OH:9])[CH2:5][CH2:4]1.I[C:31]1[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=1[NH2:33].C(=O)([O-])[O-].[Na+].[Na+]>C(C1C=CC=C(C(C)C)C=1N1C=CN(C2C(C(C)C)=CC=CC=2C(C)C)C1=[Pd-2](Cl)C1C(Cl)=CC=CN=1)(C)C.O=O>[CH3:29][N:2]([CH3:1])[C:3]1([C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[CH:23]=2)[CH2:4][CH2:5][C:6]([CH2:10][CH2:11][CH2:12][C:13]2[C:34]3[C:32](=[CH:31][CH:37]=[CH:36][CH:35]=3)[NH:33][C:14]=2[Si:15]([CH2:20][CH3:21])([CH2:16][CH3:17])[CH2:18][CH3:19])([OH:9])[CH2:7][CH2:8]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 119952-IodoanilineHCID 1317299904-Dimethylamino-4-(3-fluorophenyl)-1-(5-(triethylsilyl)pent-4-inyl)cyclohexanol

Product 1

HCID 686325504-Dimethylamino-4-(3-fluorophenyl)-1-[3-(2-(triethylsilyl)-1h-indol-3-yl)propyl]cyclohexanol

Reagents, catalysts & solvents 2

HCID 178439027HCID 178439027, compoundCatalystHCID 977OxygenSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-dimethylamino-4-(3-fluorophenyl)-1-(5-(triethylsilyl)pent-4-inyl)cyclohexanol (970 mg, 2.32 mmol), 2-iodoaniline (609 mg, 2.78 mmol), [1,3-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene]-(3-chloropyridyl)palladium(II)-chloride (PEPPSI, 156 mg, 0.23 mmol) and sodium carbonate (1.23 g, 11.6 mmol) was degasified, mixed with oxygen-free N,N-dimethylformamide (10 mL) in argon and stirred for 7 h at 100° C. The reaction mixture was then concentrated to low volume in a vacuum, the residue repeatedly taken up in toluol (10 mL) and concentrated to low volume in a vacuum again each time. This residue was distributed between ethyl acetate (30 mL) and water (30 mL), the organic phase was washed with water (2×15 mL) and sodium thiosulphate solution (2×15 mL), dried with sodium sulphate and concentrated to low volume in a vacuum. The raw product was purified by means of flash chromatography (100 g, 20×4.0 cm) with cyclohexane/ethyl acetate (4:1).

Workup

  1. concentrationThe reaction mixture was then concentrated to low volume in a vacuum
  2. concentrationconcentrated to low volume in a vacuum again each time
  3. washthe organic phase was washed with water (2×15 mL) and sodium thiosulphate solution (2×15 mL)
  4. dry with materialdried with sodium sulphate
  5. concentrationconcentrated to low volume in a vacuum
  6. customThe raw product was purified by means of flash chromatography (100 g, 20×4.0 cm) with cyclohexane/ethyl acetate (4:1)

Sources & evidence

ORD record
ord-a2343fe00de3482583b0e1064a32c25f
Source dataset
uspto-grants-2012_10
Patent number
US08288430B2

Reaction notes

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