1-Iodo-4-(trifluoromethoxy)benzene → 2,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-yn-1-ol

HRID 751200Notes

Reaction equation

HRID 751200 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[CH3:13][C:14]([CH3:20])([CH2:17][C:18]#[CH:19])[CH2:15][OH:16]>N1CCCCC1.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>[CH3:13][C:14]([CH3:20])([CH2:17][C:18]#[C:19][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1)[CH2:15][OH:16]

Participants

5

Reactant 2

HCID 27772941-Iodo-4-(trifluoromethoxy)benzeneHCID 112979482,2-Dimethylpent-4-yn-1-ol

Product 1

HCID 688212542,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-yn-1-olYield 70%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8082PiperidineSolvent2×

Conditions

Temperature
50 °C

Procedure

A mixture of 1-iodo-4-trifluoromethoxy-benzene (3.56 g, 12 mmol), Pd(PPh3)4 (578 mg, 0.5 mmol) and cuprous iodide (95 mg, 0.5 mmol) in piperidine (40 ml) was degassed (Ar) and stirred for 30 min at 50° C. under an argon atmosphere. 2,2-Dimethyl-pent-4-yn-1-ol (1.25 g, 10 mmol, 90% purity) [Magnus, Philip; Slater, Martin J.; Principe, Lawrence M. Journal of Organic Chemistry (1989), 54(21), 5148-5153] in piperidine (20 ml) was added within 60 min at 50° C. During the addition the oil bath temperature was slowly raised to 80° C. starting after 30 min. The mixture was stirred for 2 h at this temperature. The reaction mixture was cooled to ambient temperature, poured into a solution of aqueous 10% KHSO4/ice water 1/1 and extracted two times with ether. The combined extracts were washed with aqueous 10% KHSO4 and aqueous 10% NaCl and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue purified by flash chromatography (silica gel, heptane/AcOEt 2:1 to 1:1) to give 1.91 g (7 mmol, 70%) of the title compound as yellow oil.

Workup

  1. customwas degassed (Ar)
  2. additionDuring the addition the oil bath temperature
  3. temperaturewas slowly raised to 80° C.
  4. waitstarting after 30 min
  5. stirringThe mixture was stirred for 2 h at this temperature
  6. temperatureThe reaction mixture was cooled to ambient temperature
  7. extractionextracted two times with ether
  8. washThe combined extracts were washed with aqueous 10% KHSO4 and aqueous 10% NaCl
  9. dry with materialdried over sodium sulfate
  10. customThe solvent was removed under reduced pressure
  11. customthe residue purified by flash chromatography (silica gel, heptane/AcOEt 2:1 to 1:1)

Sources & evidence

ORD record
ord-0be0ed9b15a4445e94837d96637fad07
Source dataset
uspto-grants-2008_07
Patent number
US07405236B2

Reaction notes

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