Cesium carbonate → 2-(Pyridin-4-yl)-3-(4-(quinolin-2-ylmethoxy)phenyl)-1-oxaspiro[4.4]non-2-en-4-one

HRID 1258353ノート

反応式

HRID 1258353 の反応式
Br[C:2]1[C:6](=[O:7])[C:5]2([CH2:11][CH2:10][CH2:9][CH2:8]2)[O:4][C:3]=1[C:12]1[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=1.CC1(C)C(C)(C)OB([C:26]2[CH:43]=[CH:42][C:29]([O:30][CH2:31][C:32]3[CH:41]=[CH:40][C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[N:33]=3)=[CH:28][CH:27]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:15]1[CH:16]=[CH:17][C:12]([C:3]2[O:4][C:5]3([CH2:11][CH2:10][CH2:9][CH2:8]3)[C:6](=[O:7])[C:2]=2[C:26]2[CH:27]=[CH:28][C:29]([O:30][CH2:31][C:32]3[CH:41]=[CH:40][C:39]4[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=4)[N:33]=3)=[CH:42][CH:43]=2)=[CH:13][CH:14]=1

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 593548103-Bromo-2-(pyridin-4-yl)-1-oxaspiro[4.4]non-2-en-4-one

生成物 1

HCID 593547962-(Pyridin-4-yl)-3-(4-(quinolin-2-ylmethoxy)phenyl)-1-oxaspiro[4.4]non-2-en-4-one収率 6.6%

試薬・触媒・溶媒 3

HCID 44119782Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 1140Toluene溶媒

実験手順

A mixture of 3-bromo-2-(pyridin-4-yl)-1-oxaspiro[4.4]non-2-en-4-one (0.2 g, 0.68 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (0.25 g, 0.82 mmol), and Cs2CO3 (1.25 g, 6.68 mmol) in toluene (10 mL) and water (2 mL) was degassed, Pd(dppf)Cl2 (0.05 g, 0.014 mmol) was added under an inert atmosphere and again degassed. Then the reaction was refluxed for 3 h. and was filtered through a pad of Celite®, the filtrate was diluted with EtOAc (50 mL), washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 2-(pyridin-4-yl)-3-(4-(quinolin-2-ylmethoxy)phenyl)-1-oxaspiro[4.4]non-2-en-4-one (20 mg, 5%) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 8.68 (d, J=8.5 Hz, 2 H), 8.44 (d, J=7.9 Hz, 1 H), 8.02 (t, J=8.4 Hz, 2 H), 7.80 (t, J=8.2 Hz, 1 H), 7.68 (d, J=8.2 Hz, 1 H), 7.63 (t, J=8.5 Hz, 1 H), 7.48 (d, J=8.5 Hz, 2 H), 7.18 (d, J=7.4 Hz, 2 H), 7.12 (d, J=7.5 Hz, 2 H), 5.42 (s, 2 H), 2.08-1.82 (m, 8 H). MS: [M+H]: m/z=449.2. HPLC: 96.9% (RT-2.24 min), Column: Acquity BEH—C-18, 50×2.1 mm, 1.7 um. Mobile Phase: 0.025% TFA in Water (A), ACN (B), Flow rate: 0.5 ml/min (Gradient).

後処理

  1. customwas degassed
  2. customagain degassed
  3. temperatureThen the reaction was refluxed for 3 h.
  4. filtrationwas filtered through a pad of Celite®
  5. additionthe filtrate was diluted with EtOAc (50 mL)
  6. washwashed with water (20 mL), brine (20 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto obtain the crude product
  11. customThe crude material was purified via silica gel column chromatography

出典と根拠

ORDレコード
ord-e1128ca5f39e431d8be01113e1fe6f70
出典データセット
uspto-grants-2013_06
特許番号
US08466148B2

反応ノート

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