Triethylamine → (4R,5R)-4-(5-Fluoro-2-(phenylethynyl)pyridin-4-yl)-5-(2-fluorophenyl)oxazolidin-2-one

HRID 2362462Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2362462
Br[C:2]1[CH:7]=[C:6]([C@@H:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[O:11][C:10](=[O:20])[NH:9]2)[C:5]([F:21])=[CH:4][N:3]=1.C(N(CC)CC)C.[C:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)#[CH:30].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[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>[F:21][C:5]1[C:6]([C@@H:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[F:19])[O:11][C:10](=[O:20])[NH:9]2)=[CH:7][C:2]([C:30]#[C:29][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[N:3][CH:4]=1

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 11776TriphenylphosphineHCID 86673441(4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(2-fluorophenyl)oxazolidin-2-one

Produkt 1

HCID 69084026(4R,5R)-4-(5-Fluoro-2-(phenylethynyl)pyridin-4-yl)-5-(2-fluorophenyl)oxazolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysator

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A suspension of optically-enriched (4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(2-fluorophenyl)oxazolidin-2-one (38 mg, 0.107 mmol) in triethylamine (1.1 mL, 8.03 mmol) was degassed by bubbling with nitrogen for 30 min. To this was added ethynylbenzene (15 μl, 0.134 mmol) and triphenylphosphine (3.7 mg, 0.014 mmol). After bubbling 5 min longer, the reaction was treated with copper(I) iodide (0.408 mg, 2.14 μmol) and bis(triphenylphosphine)palladium(II) chloride (1.8 mg, 2.6 μmol), bubbled briefly with nitrogen, sealed, and heated at 90° C. for 5 h. The reaction was concentrated, dissolved in a minimum of dichloromethane, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, and concentrated. Column chromatography (25%→50% EtOAc/Hex) gave a mixture of the two regioisomers. This material was further purified by chiral prep HPLC (Chiralcel OD, 40% EtOH/heptane/0.1% DEA) to give 9.6 mg (23%). 1H NMR (CDCl3) δ: 8.49 (d, J=1.2 Hz, 1H), 7.76 (d, J=5.8 Hz, 1H), 7.58-7.67 (m, 2H), 7.51 (td, J=7.5, 1.5 Hz, 1H), 7.35-7.48 (m, 4H), 7.23-7.28 (m, 1H), 7.16 (ddd, J=9.8, 8.9, 0.8 Hz, 1H), 6.28 (br. s., 1H), 5.62 (d, J=5.8 Hz, 1H), 5.17 (d, J=5.8 Hz, 1H). 13C NMR (CDCl3) δ: 160.1, 158.4, 156.2, 140.8, 139.2, 135.3, 132.2, 131.4, 129.5, 128.6, 127.5, 125.2, 124.9, 124.5, 121.8, 116.2, 90.2, 87.3, 79.3, 56.6. 19F NMR (CDCl3) δ: −117.69 (d, J=8.7 Hz, 1F), −132.34 (d, J=8.7 Hz, 1F). Mass spec.: 377.2 (MH)+.

Aufarbeitung

  1. customwas degassed
  2. customby bubbling with nitrogen for 30 min
  3. customAfter bubbling 5 min longer
  4. custombubbled briefly with nitrogen
  5. customsealed
  6. concentrationThe reaction was concentrated
  7. dissolutiondissolved in a minimum of dichloromethane
  8. additiondiluted with ethyl acetate
  9. washwashed with brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated
  12. customColumn chromatography (25%→50% EtOAc/Hex) gave
  13. additiona mixture of the two regioisomers
  14. customThis material was further purified by chiral prep HPLC (Chiralcel OD, 40% EtOH/heptane/0.1% DEA)
  15. customto give 9.6 mg (23%)

Quellen und Nachweise

ORD-Eintrag
ord-3de10c19b3a846bcab28557db1f296a2
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08691821B2

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