Cesium carbonate → HCID 69084000, compound

HRID 594739Notes

Reaction equation

HRID 594739 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([OH:8])[C:3]=1[CH:9]1[N:13]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=2)[C:12](=[O:26])[CH:11]([CH3:27])[CH2:10]1.Br[CH2:29][CH2:30][O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[CH2:32]([O:31][CH2:30][CH2:29][O:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[CH:9]1[N:13]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][C:22]([F:23])([F:24])[F:25])=[CH:17][CH:16]=2)[C:12](=[O:26])[CH:11]([CH3:27])[CH2:10]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 73833Benzene, ((2-bromoethoxy)methyl)-HCID 69085281HCID 69085281, compound

Product 1

HCID 69084000HCID 69084000, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 5-(2-fluoro-6-hydroxyphenyl)-3-methyl-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one (preparation described in example 413; 50 mg; 0.13 mmol), ((2-bromoethoxy)methyl)benzene (28 mg; 0.13 mmol), potassium carbonate (36 mg; 0.26 mmol), and cesium carbonate (8.5 mg; 0.026 mmol) in anh. DMF (0.7 ml) was stirred at rt, under nitrogen, for 17 h. Water was added, and the separated aq. layer was extracted with Et2O. The mixed organic layers were washed with water, dried over anh. MgSO4, filtered and concentrated to dryness under reduced pressure affording 5-(2-(2-(benzyloxy)ethoxy)-6-fluorophenyl)-3-methyl-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one. LC-MS (conditions A): tR=1.04 min.; [M+H]+: 518.47 g/mol. A mixture of 5-(2-(2-(benzyloxy)ethoxy)-6-fluorophenyl)-3-methyl-1-(4-(trifluoromethoxy)benzyl)pyrrolidin-2-one 55 mg; 0.10 mmol), and platinum (IV) oxide hydrate PtO2 (24 mg; 0.10 mmol) in anh. MeOH (2 ml) was stirred at rt, under hydrogen atmosphere (1 atm), for 16 h. Filtration over a pad of celite, concentration to dryness under reduced pressure, and subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.84 min.; [M+H]+: 427.92 g/mol.

Workup

  1. extractionthe separated aq. layer was extracted with Et2O
  2. washThe mixed organic layers were washed with water
  3. dry with materialdried over anh. MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-a0fe66a1fdc34cf79b81d820a7c7ae17
Source dataset
uspto-grants-2016_01
Patent number
US09242970B2

Reaction notes

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