Cesium carbonate → 5-(2,6-Dimethoxyphenyl)-1-(4-((4-methylthiazol-2-yl)oxy)benzyl)pyrrolidin-2-one

HRID 594677Notes

Reaction equation

HRID 594677 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:15]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[C:14](=[O:24])[CH2:13][CH2:12]1.Br[C:26]1[S:27][CH:28]=[C:29]([CH3:31])[N:30]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC(C)(C(=O)CC(=O)C(C)(C)C)C>CN1C(=O)CCC1.Cl[Cu].C1(C)C=CC=CC=1.CCOC(C)=O.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[CH:11]1[N:15]([CH2:16][C:17]2[CH:18]=[CH:19][C:20]([O:23][C:26]3[S:27][CH:28]=[C:29]([CH3:31])[N:30]=3)=[CH:21][CH:22]=2)[C:14](=[O:24])[CH2:13][CH2:12]1

Participants

10

Reactant 4

HCID 10796Cesium carbonateHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 5515412-Bromo-4-methyl-1,3-thiazoleHCID 690819375-(2,6-Dimethoxyphenyl)-1-(4-hydroxybenzyl)pyrrolidin-2-one

Product 1

HCID 690826245-(2,6-Dimethoxyphenyl)-1-(4-((4-methylthiazol-2-yl)oxy)benzyl)pyrrolidin-2-one

Reagents, catalysts & solvents 5

HCID 62652Cuprous chlorideCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

In a microwave tube, a mixture of 5-(2,6-dimethoxyphenyl)-1-(4-hydroxybenzyl)pyrrolidin-2-one (prepared as described in example 282; 60 mg; 0.18 mmol), commercially available 2-bromo-4-methylthiazole (65 mg; 0.36 mmol), Cs2CO3 (66 mg; 0.20 mmol), CuCl (9 mg; 0.09 mmol), and commercially available 2,2,6,6-tetramethylheptane-3,5-dione (34 mg; 0.18 mmol) in anh. NMP (1 ml) was sealed and irradiated by microwave (175° C.; 10 min.). Water (1 ml), AcOEt (2 ml), and toluene (1 ml) were added, and the resulting suspension was filtered over a pad of celite. The separated organic layer was dried over anh. MgSO4, filtered, and concentrated to dryness under reduced pressure. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.83 min.; [M+H]+: 424.98 g/mol.

Workup

  1. customwas sealed
  2. customirradiated by microwave (175° C.; 10 min.)
  3. filtrationthe resulting suspension was filtered over a pad of celite
  4. dry with materialThe separated organic layer was dried over anh. MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customSubsequent purification by preparative HPLC
  8. customafforded the target compound

Sources & evidence

ORD record
ord-8ef7e825d1c84cb3be3d23f167fca88e
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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