Dimethylformamide → 4-Ethyl 5-[3-(2-carboxyacetyl)phenyl]-4-oxazolecarboxylate

HRID 1266778Notes

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][O:9][C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]([Cl:19])=[O:18])[CH:12]=1)=[O:5])[CH3:2].[CH2:20]([O:23][C:24](=[O:34])[C:25]1[CH:33]=[CH:32][CH:31]=[C:27]([C:28](O)=[O:29])[CH:26]=1)[CH:21]=[CH2:22].S(Cl)(Cl)=O.CN(C=O)C>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][O:9][C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17](=[O:18])[CH2:25][C:24]([OH:34])=[O:23])[CH:12]=1)=[O:5])[CH3:2].[CH2:20]([O:23][C:24](=[O:34])[C:25]1[CH:33]=[CH:32][CH:31]=[C:27]([C:28]([Cl:19])=[O:29])[CH:26]=1)[CH:21]=[CH2:22]

Participants

Conditions

Temperature: 90 °C

Procedure

The 5-(3-carboxyacetyl-phenyl)-oxazole-4-carboxylic acid ethyl ester was prepared from 5-(3-chlorocarbonyl-phenyl)-oxazole-4-carboxylic acid ethyl ester [prepared by the following sequence: i.) A mixture of isophthalic acid monoallyl ester (8.2 g), thionyl chloride (4.4 mL) and DMF (0.1 mL) in toluene (50 mL) was heated to 90° C. for 2 h. The mixture was evaporated in vacuum to give 3-chlorocarbonyl-benzoic acid allyl ester (9.0 g) as a light-yellow oil. ii.) To a solution of this material (9.0 g) and isocyano-acetic acid ethyl ester (4.4 mL) in THF (60 mL) was added at 0° C. Et3N (14.0 mL). The mixture was stirred at 20° C. for 2.5 h and then evaporated in vacuum. The residue was partitioned between EtOAc and brine and the organic layer was dried and evaporated in vacuum. The residual oil was chromatographed on silica gel using EtOAc/hexane as eluent to give 5-(3-allyloxycarbonyl-phenyl)-oxazole-4-carboxylic acid ethyl ester (6.9 g) as a pale-yellow oil. iii.) This material (6.9 g) was subjected to the palladium-catalysed allylester cleavage according to general procedure G (method b) to give 5-(3-carboxy-phenyl)-oxazole-4-carboxylic acid ethyl ester (6.9 g) as light brown crystals, mp 190-192° C. iv.) This carboxylic acid (2.6 g) was heated with thionyl chloride in toluene and the resulting carboxylic acid chloride was used directly in the next step.] (2.8 g) and bis(trimethylsilyl)malonate with n-BuLi in ether at −60° C. to 0° C. according to general procedure K (method c2). The crude material was transformed into the title compound by stirring in isopropenyl acetate and conc. H2SO4 according to general procedure L (method a). Obtained as pale-yellow crystals (1.4 g).

Workup

customprepared by the following sequence
customThe mixture was evaporated in vacuum

Sources & evidence

ORD record: ord-fd515eb5bf1a4d47ac7f341580acc6ca
Source dataset: uspto-grants-2003_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06548495B2

Reaction notes

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