Ethyl Acetate → 6-(2-Amino-6-chloro-pyrimidin-4-yloxy)-benzofuran-3-carboxylic acid methyl ester

HRID 556363Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:9]2[CH:10]=[CH:11][C:12]([OH:14])=[CH:13][C:8]=2[O:7][CH:6]=1)=[O:4].[NH2:15][C:16]1[N:21]=[C:20](Cl)[CH:19]=[C:18]([Cl:23])[N:17]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CCOC(C)=O>CN1C(=O)CCC1.O>[CH3:1][O:2][C:3]([C:5]1[C:9]2[CH:10]=[CH:11][C:12]([O:14][C:20]3[CH:19]=[C:18]([Cl:23])[N:17]=[C:16]([NH2:15])[N:21]=3)=[CH:13][C:8]=2[O:7][CH:6]=1)=[O:4]

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of 6.20 g (32.3 mMol) 6-hydroxy-benzofuran-3-carboxylic acid methyl ester, 8.5 g (51.8 mMol) 2-amino-4,6-dichloropyrimidine and 14.2 g (67 mMol) K3PO4 in 250 ml NMP is stirred for 3.5 h at 60° C. Then the mixture is poured into 1 l EtOAc and 1 l water, the aq. layer separated off and extracted 3 times with EtOAc. The organic phases are washed with water and brine and dried (Na2SO4). Then char coal is added, the mixture filtered and the filtrate concentrated. Trituration from ether gives the title compound: m.p.: 213-214° C. More product can be obtained from the filtrate by column chromatography (SiO2; hexane/EtOAc 2:1) as described in step 9.4.

Workup

customthe aq. layer separated off
extractionextracted 3 times with EtOAc
washThe organic phases are washed with water and brine
dry with materialdried (Na2SO4)
additionThen char coal is added
filtrationthe mixture filtered
concentrationthe filtrate concentrated

Sources & evidence

ORD record: ord-0ed7dff4d2b341c096f5fab8b3b1ca5c
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08058276B2

Reaction notes

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