Cesium carbonate → 2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)-5-(thiazol-4-yl)furan-3(2H)-one

HRID 1776387Notes

Reaction equation

HRID 1776387 reaction equation
Br[C:2]1[C:3](=[O:14])[C:4]([CH3:13])([CH3:12])[O:5][C:6]=1[C:7]1[N:8]=[CH:9][S:10][CH:11]=1.CC1(C)C(C)(C)OB([C:23]2[CH:40]=[CH:39][C:26]([O:27][CH2:28][C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)=[CH:25][CH:24]=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]>[CH3:12][C:4]1([CH3:13])[C:3](=[O:14])[C:2]([C:23]2[CH:24]=[CH:25][C:26]([O:27][CH2:28][C:29]3[CH:38]=[CH:37][C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[N:30]=3)=[CH:39][CH:40]=2)=[C:6]([C:7]2[N:8]=[CH:9][S:10][CH:11]=2)[O:5]1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 593548524-bromo-2,2-dimethyl-5-(thiazol-4-yl)furan-3(2H)-one

Product 1

HCID 593547932,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)-5-(thiazol-4-yl)furan-3(2H)-oneYield 18.9%

Reagents, catalysts & solvents 3

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

Procedure

A mixture of 4-bromo-2,2-dimethyl-5-(thiazol-4-yl)furan-3(2H)-one (0.1 g, 0.37 mmol), 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (0.164 g, 0.454 mmol), and Cs2CO3 (0.673 g, 2.06 mmol) in toluene (1 mL) and water (1 mL) was degassed and Pd(dppf)Cl2 (0.067 g, 0.082 mmol) was added under an inert atmosphere, and degassed once more. Then the reaction was refluxed for 2 h and was filtered through a pad of Celite®, the filtrate was diluted with EtOAc (10 washed with water (5 mL), brine (5 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 2,2-dimethyl-4-(4-(quinolin-2-ylmethoxy)phenyl)-5-(thiazol-4-yl) furan-3(2H)-one (30 mg, 18%) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 9.17 (s, 1H), 8.43 (d, J=8.5 Hz, 1 H), 8.30 (s, 1 H), 8.02-7.98 (m, 2 H), 7.80 (t, J=8.2 Hz, 1 H), 7.70 (d, J=8.2 Hz, 1 H), 7.62 (t, J=8.5 Hz, 1 H), 7.24 (d, J=7.5 Hz, 2 H), 7.08 (d, J=7.4 Hz, 2 H), 5.38 (s, 2 H), 1.42 (s, 6 H). MS: [M+H]: m/z=429.1. HPLC: 97.9% (RT-2.36 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. customdegassed once more
  3. temperatureThen the reaction was refluxed for 2 h
  4. filtrationwas filtered through a pad of Celite®
  5. additionthe filtrate was diluted with EtOAc (10
  6. washwashed with water (5 mL), brine (5 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-cb390bc5333f45dd89f7eddc367c8320
Source dataset
uspto-grants-2016_02
Patent number
US09265767B2

Reaction notes

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