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

HRID 2362462ノート

反応式

HRID 2362462 の反応式
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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒

反応条件

温度
90 °C

実験手順

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)+.

後処理

  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%)

出典と根拠

ORDレコード
ord-3de10c19b3a846bcab28557db1f296a2
出典データセット
uspto-grants-2014_04
特許番号
US08691821B2

反応ノート

読み込み中…