Cesium carbonate → 4-morpholino-3-(4-(quinolin-2-ylmethoxy)phenyl)furan-2(5H)-one

HRID 446804Notes

Reaction equation

HRID 446804 reaction equation
Br[C:2]1[C:3](=[O:13])[O:4][CH2:5][C:6]=1[N:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.CC1(C)C(C)(C)OB([C:22]2[CH:39]=[CH:38][C:25]([O:26][CH2:27][C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[N:29]=3)=[CH:24][CH:23]=2)O1.C([O-])([O-])=O.[Cs+].[Cs+]>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].C1(C)C=CC=CC=1.O>[O:10]1[CH2:11][CH2:12][N:7]([C:6]2[CH2:5][O:4][C:3](=[O:13])[C:2]=2[C:22]2[CH:23]=[CH:24][C:25]([O:26][CH2:27][C:28]3[CH:37]=[CH:36][C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[N:29]=3)=[CH:38][CH:39]=2)[CH2:8][CH2:9]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 583680032-((4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinolineHCID 583680173-bromo-4-morpholinofuran-2(5H)-one

Product 1

HCID 583680154-morpholino-3-(4-(quinolin-2-ylmethoxy)phenyl)furan-2(5H)-oneYield 10.4%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 22272177Toluene waterSolvent

Procedure

To a stirred solution of 3-bromo-4-morpholinofuran-2(5H)-one (300 mg, 1.20 mmol) in 2:1 toluene/H2O (8 mL) were added 2-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)methyl)quinoline (480 mg, 1.33 mmol), Cs2CO3 (1.54 g, 4.23 mmol) and Pd(dppf)Cl2 (197.5 mg, 0.24 mmol). The reaction mixture was then refluxed for 4 h, filtered and the filtrate was partitioned between water and EtOAc. The organic layer was separated, washed with water, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude material was purified via silica gel column chromatography eluting with 40% EtOAc in hexanes to afford 4-morpholino-3-(4-(quinolin-2-ylmethoxy)phenyl)furan-2(5H)-one (50 mg, 10%) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 8.42 (d, J=7.6 Hz, 1H), 8.04-7.96 (m, 2H), 7.82-7.76 (m, 1H), 7.70-7.67 (m, 1H), 7.65-7.59 (m, 1H), 7.17 (d, J=7.2 Hz, 2H), 7.05 (d, J=7.2 Hz, 2H), 5.38 (s, 2H), 4.91 (s, 2H), 3.60 (bs, 4H), 3.19 (bs, 4H). MS: M+H: m/z=403.1; M+Na: m/z=425.2 HPLC: 90%, (Condition-J).

Workup

  1. temperatureThe reaction mixture was then refluxed for 4 h
  2. filtrationfiltered
  3. customthe filtrate was partitioned between water and EtOAc
  4. customThe organic layer was separated
  5. washwashed with water
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified via silica gel column chromatography
  10. washeluting with 40% EtOAc in hexanes

Sources & evidence

ORD record
ord-b7d039c0bff8401eb9ed7892ff9cc9a7
Source dataset
uspto-grants-2013_07
Patent number
US08481534B2

Reaction notes

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