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

HRID 1480972Notes

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]

Participants

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

temperatureThen the reaction was cooled
filtrationwere filtered off
washfiltrate was washed with water, diluted NaCl solution
dry with materialdried over sodium sulfate
filtrationfiltered off
concentrationconcentrated
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

Loading…