Triethylamine → HCID 15895310, compound

HRID 842825Notes

Reaction equation

HRID 842825 reaction equation
[N:1]1([CH2:6][C@@:7]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])([OH:17])[C@H:8]([C:10]2[CH:15]=[CH:14][C:13](I)=[CH:12][CH:11]=2)[CH3:9])[CH:5]=[N:4][CH:3]=[N:2]1.[CH3:26][N:27]1[C:31]([CH:32]=[CH2:33])=[CH:30][CH:29]=[N:28]1.C(N(CC)CC)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:1]1([CH2:6][C@@:7]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=2[F:25])([OH:17])[C@H:8]([C:10]2[CH:15]=[CH:14][C:13](/[CH:33]=[CH:32]/[C:31]3[N:27]([CH3:26])[N:28]=[CH:29][CH:30]=3)=[CH:12][CH:11]=2)[CH3:9])[CH:5]=[N:4][CH:3]=[N:2]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 80271Tri-o-tolylphosphineHCID 13036321HCID 13036321, compoundHCID 15895309HCID 15895309, compound

Product 1

HCID 15895310HCID 15895310, compoundYield 64.7%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolvent

Procedure

A stirred solution of (2R,3S)-1-(1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-(4-iodophenyl)butan-2-ol (Preparation 12; 0.5 g, 1.1 mmol), 1-methyl-5-vinylpyrazole (Preparation 17; 0.14 g, 1.3 mmol), triethylamine (0.25 ml, 2 mmol), palladium acetate (130 mg, 0.6 mmol) and tri-o-tolylphosphine (340 mg, 1.2 mmol) in acetonitrile (25 ml) was heated under reflux for 1 hour and then evaporated under reduced pressure. The residue was partitioned between ethyl acetate (100 ml) and saturated aqueous sodium bicarbonate solution (50 ml), then the organic phase separated, washed with saturated brine (30 ml), dried (Na2SO4) and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel, using an elution gradient of hexane:propan-2-ol (90:10 to 75:25), to give the title compound (0.31 g) as a white solid, m.p. 81-83° C., after crystallisation from aqueous ethanol. [α]D25 −55° (c=0.1, CH3OH).

Workup

  1. temperatureunder reflux for 1 hour
  2. customevaporated under reduced pressure
  3. customThe residue was partitioned between ethyl acetate (100 ml) and saturated aqueous sodium bicarbonate solution (50 ml)
  4. customthe organic phase separated
  5. washwashed with saturated brine (30 ml)
  6. dry with materialdried (Na2SO4)
  7. customevaporated under reduced pressure
  8. customThe crude product was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-d7d3784e1eaa42d08e96591172e291f7
Source dataset
uspto-grants-2002_04
Patent number
US06376526B1

Reaction notes

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