Triphenylphosphine → HCID 86712699, compound

HRID 1779055Notes

Reaction equation

HRID 1779055 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Br[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[C:22]=1[CH2:31][C:32]([O:34][CH3:35])=[O:33].CCN(C(C)C)C(C)C.[CH2:45]([Si:47]([C:52]#[CH:53])([CH2:50][CH3:51])[CH2:48][CH3:49])[CH3:46]>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:48]([Si:47]([C:45]#[C:46][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[C:22]=1[CH2:31][C:32]([O:34][CH3:35])=[O:33])([CH2:52][CH3:53])[CH2:50][CH3:51])[CH3:49]

Participants

8

Reactant 4

HCID 11776Triphenylphosphine2×HCID 81531Diisopropylethylamine2×HCID 637947(Triethylsilyl)acetylene2×HCID 86712698HCID 86712698, compound

Product 1

HCID 86712699HCID 86712699, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 178418476HCID 178418476, compoundCatalyst2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
90 °C

Procedure

A mixture of CuI (0.005 g, 0.03 mmol), PdCl2(PPh3)2 (0.009 g, 0.01 mmol), PPh3 (0.017 g, 0.065 mmol) and methyl 2-(2-bromo-6-(trifluoromethyl)phenyl)acetate (A91) (0.213 g, 0.717 mmol) in DMF (2.0 mL) was degassed with nitrogen for several minutes before the addition of DIPEA (2.00 mL, 11.5 mmol) and (triethylsilyl)acetylene (0.50 mL, 2.8 mmol). The resulting mixture was then degassed with nitrogen before heating under microwave irradiation at 90° C. for 2×20 minutes. The volatiles were evaporated under reduced pressure and the residue purified using silica gel column chromatography (0-10% EtOAc in petroleum benzine 40-60° C.) to give a mixture of product and starting material. To this material, CuI (0.013 g, 0.068 mmol), PdCl2(PPh3)2 (0.013 g, 0.019 mmol), PPh3 (0.030 g, 0.114 mmol), DMF (4.0 mL), DIPEA (2.00 mL, 11.5 mmol) and (triethylsilyl)acetylene (0.50 mL, 2.8 mmol) were added. The resulting mixture was heated at 100° C. for 30 minutes then concentrated under reduced pressure and the residue purified using silica gel column chromatography (Biotage Isolera, SiO2 cartridge, 5-10% EtOAc in petroleum benzine 40-60° C.) to give the title compound A92 (0.175 g, 69%); 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J=7.7 Hz, 1H), 7.62 (d, J=7.9 Hz, 1H), 7.35 (m, 1H), 4.09 (m, 2H), 3.68 (s, 3H), 1.03 (t, J=7.9 Hz, 9H), 0.67 (q, J=7.9 Hz, 6H).

Workup

  1. customThe resulting mixture was then degassed with nitrogen
  2. customThe volatiles were evaporated under reduced pressure
  3. customthe residue purified
  4. customsilica gel column chromatography (0-10% EtOAc in petroleum benzine 40-60° C.)
  5. customto give
  6. additiona mixture of product
  7. temperatureThe resulting mixture was heated at 100° C. for 30 minutes
  8. concentrationthen concentrated under reduced pressure
  9. customthe residue purified
  10. customsilica gel column chromatography (Biotage Isolera, SiO2 cartridge, 5-10% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-a67866eb2d2a45ada4db666f2c6b963a
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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