Triethylamine → HCID 69747974, compound

HRID 2301068Notes

Reaction equation

HRID 2301068 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:20][Si:21]([C:24]#[CH:25])([CH3:23])[CH3:22].C(N(CC)CC)C.Br[C:34]1[CH:39]=[C:38]([S:40]([C:43]2[CH:48]=[CH:47][C:46]([S:49]([CH3:52])(=[O:51])=[O:50])=[CH:45][CH:44]=2)(=[O:42])=[O:41])[CH:37]=[CH:36][C:35]=1[NH:53][C:54](=[O:62])[C@:55]([OH:61])([CH3:60])[C:56]([F:59])([F:58])[F:57]>C1COCC1.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.[Cu]I.C(OCC)(=O)C>[CH3:20][Si:21]([CH3:23])([CH3:22])[C:24]#[C:25][C:34]1[CH:39]=[C:38]([S:40]([C:43]2[CH:44]=[CH:45][C:46]([S:49]([CH3:52])(=[O:51])=[O:50])=[CH:47][CH:48]=2)(=[O:42])=[O:41])[CH:37]=[CH:36][C:35]=1[NH:53][C:54](=[O:62])[C@:55]([OH:61])([CH3:60])[C:56]([F:58])([F:59])[F:57]

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 66111Trimethylsilylacetylene2×HCID 54101286HCID 54101286, compound

Product 1

HCID 69747974HCID 69747974, compoundYield 89%

Reagents, catalysts & solvents 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Bis(triphenylphosphine)palladium(II) chloride (0.01 g), triphenylphosphine (0.0038 g), trimethylsilylacetylene (0.17 ml), triethylamine (0.16 ml) and copper(I) iodide (0.0013 g) were added to a solution of (R)-N-[2-bromo-4-(4-mesylphenylsulphonyl)phenyl]-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 140) (0.311 g) in anhydrous THF (10 ml) under argon. The mixture was heated at 50° C. for 3 hours then more bis(triphenylphosphine) palladium(II) chloride (0.01 g) and trimethylsilylacetylene (0.17 ml) were added and heating was continued for a further 3 hours. The reaction mixture was allowed to cool, ethyl acetate (50 ml) was added and the mixture was filtered through a pad of diatomaceous earth which was washed with ethyl acetate (3×20 ml). The filtrates were combined and volatile material was removed by evaporation. The residue was purified by chromatography eluting with 10-40% ethyl acetate/iso-hexane to give the title compound (in 89% yield) as a solid. NMR (CDCl3): 0.29 (s, 9H), 1.74 (s, 3H), 3.05 (s, 3H), 3.69 (s, 1H), 7.88-7.92 (m, 1H), 8.02 (d, 1H), 8.05-8.13 (m, 4H), 8.61 (d, 1H), 9.46 (s, 1H); MS (ESP−): 546.

Workup

  1. temperatureheating
  2. temperatureto cool
  3. filtrationthe mixture was filtered through a pad of diatomaceous earth which
  4. washwas washed with ethyl acetate (3×20 ml)
  5. customvolatile material was removed by evaporation
  6. customThe residue was purified by chromatography
  7. washeluting with 10-40% ethyl acetate/iso-hexane

Sources & evidence

ORD record
ord-071587a7bc0d4411af64f08787105340
Source dataset
uspto-grants-2002_12
Patent number
US06498275B1

Reaction notes

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