Dichloromethane → 4-(2-Fluoro-5-((triisopropylsilyl)ethynyl)phenyl)morpholine

HRID 2240999Notes

Reaction equation

HRID 2240999 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:14])=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:7]=1.[CH:15]([Si:18]([C:25]#[CH:26])([CH:22]([CH3:24])[CH3:23])[CH:19]([CH3:21])[CH3:20])([CH3:17])[CH3:16].ClCCl>C(N(CC)CC)C.[Cu](I)I.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:14][C:5]1[CH:4]=[CH:3][C:2]([C:26]#[C:25][Si:18]([CH:15]([CH3:17])[CH3:16])([CH:22]([CH3:24])[CH3:23])[CH:19]([CH3:21])[CH3:20])=[CH:7][C:6]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Participants

7

Reactant 3

HCID 6344DichloromethaneHCID 2734682(Triisopropylsilyl)acetyleneHCID 593053644-(5-Bromo-2-fluorophenyl)morpholine

Product 1

HCID 575824344-(2-Fluoro-5-((triisopropylsilyl)ethynyl)phenyl)morpholineYield 99.6%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8471TriethylamineSolvent

Procedure

To a CEM snap top microwave vial (10 ml) equipped with a magnetic stir bar (3×10 mm) was added 4-(5-bromo-2-fluorophenyl)morpholine (390 mg, 1.50 mmol) in triethylamine (1.5 mL). Copper iodide (12 mg, 0.060 mmol), Tetrakis(triphenylphosphine) palladium (35 mg, 0.030 mmol) and triisopropylsilyl-acetylene (0.390 mg, 2.14 mmol) were added at room temperature. The reaction was capped and irradiated in a CEM Explorer microwave at 80° C. for 30 minutes then forced air-cooled. The crude material was loaded onto silica gel and chased with dichloromethane. Purification by chromatography (hexanes) afforded 540 mg of an oil (quant); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06-1.10 (m, 21H) 3.00 (t, J=4.6 Hz, 4H) 3.71 (t, J=4.6 Hz, 4H) 7.01 (dd, J=8.5, 2.0 Hz, 1H) 7.08 (ddd, J=4.9, 2.9, 2.6 Hz, 1H) 7.11-7.18 (m, 1H); MS (ES) m/z 362.2 [M+H]+

Workup

  1. customTo a CEM snap top microwave vial (10 ml) equipped with a magnetic stir bar (3×10 mm)
  2. customThe reaction was capped
  3. customirradiated in a CEM Explorer microwave at 80° C. for 30 minutes
  4. temperaturethen forced air-cooled
  5. customPurification by chromatography (hexanes)

Sources & evidence

ORD record
ord-404c33bf808645e287be7bf06cdf89a6
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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