Acetic Acid → 3-{[(Benzyloxy)carbonyl]amino}-6-fluoro-7-vinylquinoline-2-carboxylic acid

HRID 924381ノート

反応式

HRID 924381 の反応式
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:24]([O:26]CC)=[O:25])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][C:18]([F:22])=[C:17](Br)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:37](B1OC(C)(C)C(C)(C)O1)=[CH2:38].CC(O)=O>O1CCOCC1.CC(C1C=C(C(C)C)C(C2C=CC=C(P(C3CCCCC3)C3CCCCC3)C=2)=C(C(C)C)C=1)C.C1C=[C-]C(C2C(N)=CC=CC=2)=CC=1.Cl[Pd+]>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:24]([OH:26])=[O:25])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][C:18]([F:22])=[C:17]([CH:37]=[CH2:38])[CH:16]=2)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 62657Potassium Phosphate, TribasicHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86726865Ethyl 3-{[(benzyloxy)carbonyl]amino}-7-bromo-6-fluoroquinoline-2-carboxylate

生成物 1

HCID 867268643-{[(Benzyloxy)carbonyl]amino}-6-fluoro-7-vinylquinoline-2-carboxylic acid収率 74%

試薬・触媒・溶媒 2

HCID 72376365[2-(2-Aminophenyl)phenyl]-chloro-palladium dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphane触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
90 °C

実験手順

To a screw-cap vial equipped with a magnetic stir bar, ethyl 3-{[(benzyloxy)carbonyl]amino}-7-bromo-6-fluoroquinoline-2-carboxylate (252.8 mg, 0.5652 mmol), chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (Aldrich, 22.8 mg, 0.0289 mmol) and K3PO4 (392.6 mg, 1.850 mmol) were added. The vial was sealed with a Teflon®-lined septum, and was then evacuated and backfilled with nitrogen three times. A solution of vinylboronic acid pinacol ester (146.9 mg, 0.9538 mmol) in 1,4-dioxane (4.0 mL) was added via a syringe, followed by deoxygenated water (2.0 mL). The resulting mixture was heated at 90° C. for 1 h, then allowed to cool to room temperature. Water (50 mL) was added followed by AcOH (379 mg, 6.32 mmol) to adjust the pH to 5. The mixture was extracted with EtOAc (3×50 mL). The combined organic extract was washed with brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by flash chromatography on silica gel (0-10% MeOH in DCM) to give the sub-title compound as a yellow solid (153.2 mg, 74%). LCMS calc. for C20H16FN2O4 (M+H)+: m/z=367.1. found 367.1.

後処理

  1. customTo a screw-cap vial equipped with a magnetic stir bar
  2. customwas then evacuated
  3. customby deoxygenated water (2.0 mL)
  4. temperatureto cool to room temperature
  5. additionWater (50 mL) was added
  6. extractionThe mixture was extracted with EtOAc (3×50 mL)
  7. extractionThe combined organic extract
  8. washwas washed with brine (100 mL)
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue was purified by flash chromatography on silica gel (0-10% MeOH in DCM)

出典と根拠

ORDレコード
ord-6da929b6f5ea42aaa87c235e23738c93
出典データセット
uspto-grants-2016_03
特許番号
US09278950B2

反応ノート

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