Triethylamine → 1-Difluoromethoxy-4-{3-[3-(2-fluoro-ethyl)-cyclobutyl]phenyl-ethynyl}benzene

HRID 2240963Notes

Reaction equation

HRID 2240963 reaction equation
[F:1][CH2:2][CH2:3][CH:4]1[CH2:7][CH:6]([C:8]2[CH:9]=[C:10]([C:14]#[C:15][Si](C(C)C)(C(C)C)C(C)C)[CH:11]=[CH:12][CH:13]=2)[CH2:5]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Br[C:45]1[CH:50]=[CH:49][C:48]([O:51][CH:52]([F:54])[F:53])=[CH:47][CH:46]=1.C(N(CC)CC)C>C1COCC1.[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:53][CH:52]([F:54])[O:51][C:48]1[CH:49]=[CH:50][C:45]([C:15]#[C:14][C:10]2[CH:11]=[CH:12][CH:13]=[C:8]([CH:6]3[CH2:5][CH:4]([CH2:3][CH2:2][F:1])[CH2:7]3)[CH:9]=2)=[CH:46][CH:47]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 27370071-Bromo-4-(difluoromethoxy)benzeneHCID 59305330{3-[3-(2-Fluoro-ethyl)-cyclobutyl]-phenylethynyl}-triisopropyl-silane

Product 1

HCID 593053551-Difluoromethoxy-4-{3-[3-(2-fluoro-ethyl)-cyclobutyl]phenyl-ethynyl}benzeneYield 53.1%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

{3-[3-(2-Fluoro-ethyl)-cyclobutyl]-phenylethynyl}-triisopropyl-silane (349 mg, 0.973 mmol) was dissolved in THF (2 ml) and treated with a 1M solution of tetrabutylammonium fluoride (TBAF) in THF (2 ml) at room temperature. The crude product obtained from aqueous work-up was placed in a CEM snap top microwave vial and combined with 1-Bromo-4-Difluoromethoxybenzene (300 mg 1.30 mmol), copper iodide (35 mg, 0.131 mmol), tetrakis(triphenylphosphine)palladium (70 mg, 0.060 mmol) and triethylamine (4.3 g, 42.5 mmol). The vial was quickly agitated then irradiated in a CEM Explorer™ microwave instrument for 30 minutes at 80° C. Purification by column chromatography (gradient; 0%, then 5% EtOAc in hexanes) afforded an oil 178 mg (53%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.80 (m, 2H) 1.85-2.11 (m, 2H) 2.17-2.36 (m, 2H) 2.38-2.43 (m, 1H) 3.28-3.65 (m, 1H) 4.24-4.52 (m, 2H) 7.01-7.47 (m, 5H) 7.18 (d, J=8.8 Hz, 2H) 7.58 (d, J=8.8 Hz, 2H).

Workup

  1. customThe crude product obtained from aqueous work-up
  2. customthen irradiated in a CEM Explorer™ microwave instrument for 30 minutes at 80° C
  3. customPurification by column chromatography (gradient

Sources & evidence

ORD record
ord-bd22702726aa40b88069c852fc24360a
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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