1-Bromo-4-(difluoromethoxy)benzene → HCID 59305326, compound

HRID 2241001Notes

Reaction equation

HRID 2241001 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]([F:15])=[C:7]([N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:8]=1)#[CH:2].Br[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH:24]([F:26])[F:25])=[CH:19][CH:18]=1.[Al]>C(N(CC)CC)C.C(OCC)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:25][CH:24]([F:26])[O:23][C:20]1[CH:21]=[CH:22][C:17]([C:2]#[C:1][C:3]2[CH:4]=[CH:5][C:6]([F:15])=[C:7]([N:9]3[CH2:14][CH2:13][O:12][CH2:11][CH2:10]3)[CH:8]=2)=[CH:18][CH:19]=1

Participants

8

Reactant 3

HCID 27370071-Bromo-4-(difluoromethoxy)benzeneHCID 5359268AluminumHCID 86627925HCID 86627925, compound

Product 1

HCID 59305326HCID 59305326, compoundYield 96%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8471TriethylamineSolvent

Procedure

In a 0.5-2 ml Biotage conical microwave vial equipped with magnetic spin vane was dissolved 4-(5-ethynyl-2-fluorophenyl)morpholine (540 mg, 1.50 mmol) in triethylamine (1.5 mL). Copper iodide (54 mg, 0.283 mmol) and Tetrakis(triphenylphosphine) palladium (105 mg, 0.091 mmol) were added. Lastly 1-bromo-4-(difluoromethoxy)benzene (0.750 g, 3.36 mmol) was added, the vial was covered with a teflon septa, an aluminum cap was crimped in place, and the assembly was set on a Biotage Emrys microwave instrument to irradiate at 80° C. for 30 minutes. The crude reaction was diluted with diethylether, washed with saturated ammonium chloride, and purified via column chromatography on a Yamazen W-Prep 2XY using 25% EtOAc in hexanes. Concentration by rotary evaporation afforded 500 mg of oil (96%); 1H NMR (400 MHz, DMSO-d6) δ ppm 3.03 (t, J=4.6 Hz, 4H) 3.73 (t, J=4.6 Hz, 4H) 7.13-7.14 (m, 1H) 7.16 (d, J=2.6 Hz, 1H) 7.17-7.19 (m, 2H) 7.22 (d, J=8.8 Hz, 2H) 7.24 (t, J=73.8 Hz, 1H) 7.60 (d, J=8.8 Hz, 2H); MS (ES) m/z 348.2 [M+H]+

Workup

  1. customIn a 0.5-2 ml Biotage conical microwave vial equipped with magnetic spin vane
  2. customto irradiate at 80° C. for 30 minutes
  3. customThe crude reaction
  4. washwashed with saturated ammonium chloride
  5. custompurified via column chromatography on a Yamazen W-Prep
  6. concentrationConcentration
  7. customby rotary evaporation

Sources & evidence

ORD record
ord-39eab634cd314916a628b7fc5a031e38
Source dataset
uspto-grants-2010_05
Patent number
US07723368B2

Reaction notes

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