Cesium carbonate → 4-(2-Chloro-5-fluoro-phenoxy)-2-{[(2,4-dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-benzoic acid ethyl ester

HRID 1480990Notes

Reaction equation

HRID 1480990 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][C:6]=1[CH2:12][N:13](OC1C=CC(OC)=CC=1OC)[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:2].[Cl:32][C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][C:34]=1[OH:40].C[C:42]([CH3:53])([C:44](=O)[CH2:45][C:46](=[O:51])[C:47]([CH3:50])(C)C)C.[C:54](=[O:57])([O-])[O-].[Cs+].[Cs+].[CH3:60]N1C(=O)CCC1>CCOC(C)=O.Cl[Cu]>[CH2:1]([O:3][C:4](=[O:31])[C:5]1[CH:10]=[CH:9][C:8]([O:40][C:34]2[CH:35]=[C:36]([F:39])[CH:37]=[CH:38][C:33]=2[Cl:32])=[CH:7][C:6]=1[CH2:12][N:13]([CH2:53][C:42]1[CH:44]=[CH:45][C:46]([O:51][CH3:60])=[CH:47][C:50]=1[O:57][CH3:54])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:2]

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 13387N-methyl-2-pyrrolidoneHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 27245222-Chloro-5-fluorophenolHCID 898132434-Bromo-2-{[(2,4-dimethoxy-phenoxy)-ethoxycarbonylmethyl-amino]-methyl}-benzoic acid ethyl ester

Product 1

HCID 898131744-(2-Chloro-5-fluoro-phenoxy)-2-{[(2,4-dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-benzoic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 4-bromo-2-{[(2,4-dimethoxy-phenoxy)-ethoxycarbonylmethyl-amino]-methyl}-benzoic acid ethyl ester (3.37 g), 2-chloro-5-fluoro-phenol (1.5 g), CuCl (337 mg), 2,2,6,6-tetramethyl-heptane-3,5-dione (TMHD, 0.27 mL), cesium carbonate (3.33 g) in NMP (6 mL) was heated at 130° C. for 24 h. The reaction was cooled, diluted with EtOAc, solids were filtered off, filtrate was washed with water, diluted NaCl solution, dried over sodium sulfate, filtered off, concentrated, the residue was column purified to give the desired product (1.59 g). LC MS ESI+: 561 (M+1)+.

Workup

  1. temperatureThe reaction was cooled
  2. filtrationwere filtered off
  3. washfiltrate was washed with water, diluted NaCl solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered off
  6. concentrationconcentrated
  7. custompurified

Sources & evidence

ORD record
ord-3a3f1e47e7d647d3a89c5df6d204a866
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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