Hydrochloric Acid → methyl 5-(6-bromo-1-oxo-1H-isochromen-3-yl)pentanoate

HRID 927262Notes

Reaction equation

HRID 927262 reaction equation
[CH3:1][O:2][C:3](=[O:11])[CH2:4][CH2:5][CH2:6][CH2:7][C:8]([OH:10])=O.[Br:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[C:15]([CH2:22]C(O)=O)[CH:14]=1.Cl>C1COCC1>[Br:12][C:13]1[CH:14]=[C:15]2[C:16](=[CH:20][CH:21]=1)[C:17](=[O:18])[O:10][C:8]([CH2:7][CH2:6][CH2:5][CH2:4][C:3]([O:2][CH3:1])=[O:11])=[CH:22]2

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 12328monoMethyl adipateHCID 534401324-Bromo-2-(carboxymethyl)benzoic acid

Product 1

HCID 90095220methyl 5-(6-bromo-1-oxo-1H-isochromen-3-yl)pentanoateYield 11.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred mixture of adipic acid monomethyl ester (9.27 g, 57.9 mmol, 1.50 equiv.) in THF (50 mL) was added N,N′-carbonyldiimidazole (9.39 g, 57.9 mmol, 1.50 equiv.) and the mixture was stirred at room temperature. After stirring for 30 min, the reaction mixture was cooled to 0° C. followed by dropwise addition of 4-bromo-2-(carboxymethyl)benzoic acid (10.0 g, 38.6 mmol) in THF (25 mL). The reaction was stirred gradually from 0° C. to room temperature for 48 h. Upon completion of the reaction, 0.5 N HCl (25 mL) solution was added and extracted with EtOAc (2×25 mL). The organic layer was washed with aqueous sat. NaHCO3, dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with 0-15% EtOAc/hexanes to give 1.5 g of methyl 5-(6-bromo-1-oxo-1H-isochromen-3-yl)pentanoate as a white solid.

Workup

  1. stirringAfter stirring for 30 min
  2. temperaturethe reaction mixture was cooled to 0° C.
  3. stirringThe reaction was stirred gradually from 0° C. to room temperature for 48 h
  4. additionwas added
  5. extractionextracted with EtOAc (2×25 mL)
  6. washThe organic layer was washed with aqueous sat. NaHCO3
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe residue was purified by column chromatography on silica gel eluting with 0-15% EtOAc/hexanes

Sources & evidence

ORD record
ord-b8cffd0f5d52495d88571b42fee1bed9
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

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