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3-Hydroxypyridine → 2-{[(2,4-Dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-4-(pyridin-3-yloxy)-benzoic acid ethyl ester

HRID 1480972
Notes
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Reaction equation

HRID 1480972 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].[N:32]1[CH:37]=[CH:36][CH:35]=[C:34]([OH:38])[CH:33]=1.C[C:40]([CH3:51])([C:42](=O)[CH2:43][C:44](=[O:49])[C:45]([CH3:48])(C)C)C.[C:52](=[O:55])([O-])[O-].[Cs+].[Cs+].[CH3:58]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:38][C:34]2[CH:33]=[N:32][CH:37]=[CH:36][CH:35]=2)=[CH:7][C:6]=1[CH2:12][N:13]([CH2:51][C:40]1[CH:42]=[CH:43][C:44]([O:49][CH3:58])=[CH:45][C:48]=1[O:55][CH3:52])[CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:2]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 79713-HydroxypyridineHCID 10796Cesium carbonateHCID 13387N-methyl-2-pyrrolidoneHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 898132434-Bromo-2-{[(2,4-dimethoxy-phenoxy)-ethoxycarbonylmethyl-amino]-methyl}-benzoic acid ethyl ester

Product 1

HCID 89813094
2-{[(2,4-Dimethoxy-benzyl)-ethoxycarbonylmethyl-amino]-methyl}-4-(pyridin-3-yloxy)-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 (3.292 g), pyridin-3-ol (887 mg), CuCl (330 mg), 2,2,6,6-tetramethyl-heptane-3,5-dione (TMHD, 0.26 mL), cesium carbonate (3.26 g) in NMP (6 mL) was heated at 130° C. for 24 h. Then 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 (1.71 g). LC MS ESI+: 509 (M+1)+.

Workup

  1. temperatureThen the 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-5d9be79dc7264d8fb8ea3c70d1926b75
Source dataset
uspto-grants-2016_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09409892B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes