3,4,5,6-Tetrahydrophthalic anhydride → 1-[2-Chloro-4-fluoro-5-(1,2,3,4,5,6-hexahydro-1,3-dioxo-isoindolyl)-phenylthio]-cyclobutanecarboxylic acid methyl ester

HRID 1646456Notes

Reaction equation

HRID 1646456 reaction equation
[CH3:1][O:2][C:3]([C:5]1([S:9][C:10]2[CH:15]=[C:14]([NH2:16])[C:13]([F:17])=[CH:12][C:11]=2[Cl:18])[CH2:8][CH2:7][CH2:6]1)=[O:4].[C:19]1(=O)[O:24][C:22](=[O:23])[C:21]2[CH2:25][CH2:26][CH2:27][CH2:28][C:20]1=2>C(O)(=O)C>[CH3:1][O:2][C:3]([C:5]1([S:9][C:10]2[CH:15]=[C:14]([N:16]3[C:22](=[O:23])[CH:21]4[C:20](=[CH:28][CH2:27][CH2:26][CH2:25]4)[C:19]3=[O:24])[C:13]([F:17])=[CH:12][C:11]=2[Cl:18])[CH2:8][CH2:7][CH2:6]1)=[O:4]

Participants

4

Reactant 2

HCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 544812611-(5-Amino-2-chloro-4-fluorophenylthio)-cyclobutanecarboxylic acid methyl ester

Product 1

HCID 678545351-[2-Chloro-4-fluoro-5-(1,2,3,4,5,6-hexahydro-1,3-dioxo-isoindolyl)-phenylthio]-cyclobutanecarboxylic acid methyl esterYield 62.1%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 4.4 g of 1-(5-amino-2-chloro-4-fluorophenylthio)-cyclobutanecarboxylic acid methyl ester and 2.4 g of 3,4,5,6-tetrahydrophthalic anhydride in 60 ml of glacial acetic acid is heated under reflux for 5 hours while stirring. The reaction mixture is then introduced into ice-water and the resulting glutinous product is extracted with ethyl acetate. After drying the organic phase over sodium sulfate and concentrating by evaporation in vacuo, petroleum ether is added to the resulting residue and the substance solidifies. Filtering yields 4 g of 1-[2-chloro-4-fluoro-5-(1,2,3,4,5,6-hexahydro-1,3-dioxo-isoindolyl)-phenylthio]-cyclobutanecarboxylic acid methyl ester having a melting point of +98° C.

Workup

  1. temperatureis heated
  2. temperatureunder reflux for 5 hours
  3. extractionthe resulting glutinous product is extracted with ethyl acetate
  4. dry with materialAfter drying the organic phase over sodium sulfate
  5. concentrationconcentrating by evaporation in vacuo, petroleum ether
  6. additionis added to the resulting residue
  7. filtrationFiltering

Sources & evidence

ORD record
ord-be138bb298df4b7d80d5d89b37dc8675
Source dataset
uspto-grants-1993_01
Patent number
US05180418

Reaction notes

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