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

HRID 2240967Notes

Reaction equation

HRID 2240967 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH:5]1[CH2:8][CH:7]([C:9]2[CH:10]=[C:11]([C:15]#[C:16][Si](C(C)C)(C(C)C)C(C)C)[CH:12]=[CH:13][CH:14]=2)[CH2:6]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Br[C:46]1[CH:51]=[CH:50][C:49]([O:52][CH:53]([F:55])[F:54])=[CH:48][CH:47]=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:54][CH:53]([F:55])[O:52][C:49]1[CH:50]=[CH:51][C:46]([C:16]#[C:15][C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([CH:7]3[CH2:6][CH:5]([CH2:4][CH2:3][O:2][CH3:1])[CH2:8]3)[CH:10]=2)=[CH:47][CH:48]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2724141Tetrabutylammonium FluorideHCID 27370071-Bromo-4-(difluoromethoxy)benzeneHCID 59305302{3-[3-(2-Methoxy-ethyl)-cyclobutyl]-phenylethynyl}-triisopropyl-silane

Product 1

HCID 593053721-Difluoromethoxy-4-{3-[3-(2-methoxy-ethyl)-cyclobutyl]phenyl-ethynyl}benzeneYield 91.7%

Reagents, catalysts & solvents 3

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

Procedure

{3-[3-(2-methoxy-ethyl)-cyclobutyl]-phenylethynyl}-triisopropyl-silane (1.00 g, 2.70 mmol) was dissolved in THF (5 ml) and treated with a 1M solution of tetrabutylammonium fluoride (TBAF) in THF (5 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 (1.20 gm, 5.38 mmol), copper iodide (70 mg, 0.262 mmol), tetrakis(triphenylphosphine)palladium (140 mg, 0.120 mmol) and triethylamine (5.8 g, 98 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%-10% EtOAc in hexanes) afforded an oil 882 mg (46%). This material was used in next step without further characterization.

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; 0%-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f338a79dbf99473fbc4f5b642bec9076
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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