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

HRID 655475Notes

Reaction equation

HRID 655475 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

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, 2H), 8.44 (d, J=7.9 Hz, 1H), 8.02 (t, J=8.4 Hz, 2H), 7.80 (t, J=8.2 Hz, 1H), 7.68 (d, J=8.2 Hz, 1H), 7.63 (t, J=8.5 Hz, 1H), 7.48 (d, J=8.5 Hz, 2H), 7.18 (d, J=7.4 Hz, 2H), 7.12 (d, J=7.5 Hz, 2H), 5.42 (s, 2H), 2.08-1.82 (m, 8H). 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).

Workup

  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

Sources & evidence

ORD record
ord-0e718d0b8da4495386d6581d01fac42e
Source dataset
uspto-grants-2011_12
Patent number
US08071595B2

Reaction notes

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