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

HRID 2362462노트

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HRID 2362462 반응식
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

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매

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온도
90 °C

실험 절차

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)+.

후처리

  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%)

출처 및 근거

ORD 기록
ord-3de10c19b3a846bcab28557db1f296a2
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08691821B2

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