1-Butanol → HCID 178450858, compound

HRID 523699Notes

Reaction equation

HRID 523699 reaction equation
[Na].[CH3:2][O:3][C:4](=[O:25])[CH2:5][N:6]1[C:14](=[O:15])[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([O:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH:12]=2)[C:7]1=[O:24].Cl.[CH2:27](O)[CH2:28][CH2:29]C>>[CH2:2]([O:3][C:4]([C:5]1[N:6]=[C:14]([OH:15])[C:13]2[C:8]([C:7]=1[OH:24])=[CH:9][CH:10]=[C:11]([O:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH:12]=2)=[O:25])[CH2:27][CH2:28][CH3:29]

Participants

5

Reactant 4

HCID 2631-Butanol2×HCID 313Hydrochloric AcidHCID 5360545SodiumHCID 66713045[5-(4-Fluoro-phenoxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-acetic acid methyl ester

Product 1

HCID 178450858HCID 178450858, compound

Conditions

Temperature
70 °C

Procedure

Sodium (7.2 g, 310 mmol) was dissolved in n-butanol (300 ml) with stirring at 70° C. Afterwards, the temperature was raised to 95-100° C. and a solution of [5-(4-Fluoro-phenoxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-acetic acid methyl ester (49.4 g, 150 mmol) in hot n-butanol (300 ml) was added with vigorous stirring. The mixture was stirred for another 90 min at 95-100° C. and was then allowed to cool to 60° C. with stirring before 2N HCl (160 ml) was added. The mixture was stirred vigorously for 30 min and was then allowed to cool to ambient temperature. Subsequently, the mixture was submitted to vacuum filtration. The filter cake was washed thoroughly with water and dried in vacuo at 70° C. to give a pale yellow solid. Purification by flash column chromatography on silica gel using CH2Cl2 EtOAc=98 2 as the eluent gave the title compound (14.4 g, first fraction); 1H NMR (CDCl3) δ=8.40 (br s, 1H), 8.14 (d, 1H), 7.80 (d, 1H), 7.42 to 7.48 (m, 1H), 7.04 to 7.14 (m, 4H), 4.39 (t, 2H), 1.70 to 1.85 (m, 2H), 1.37 to 1.55 (m, 2H), 0.99 (t, 3H).

Workup

  1. temperatureAfterwards, the temperature was raised to 95-100° C.
  2. stirringThe mixture was stirred for another 90 min at 95-100° C.
  3. temperatureto cool to 60° C.
  4. additionwas added
  5. stirringThe mixture was stirred vigorously for 30 min
  6. temperatureto cool to ambient temperature
  7. filtrationSubsequently, the mixture was submitted to vacuum filtration
  8. washThe filter cake was washed thoroughly with water
  9. customdried in vacuo at 70° C.
  10. customto give a pale yellow solid
  11. customPurification by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-52fff0083425418fac2409bde14935d0
Source dataset
uspto-grants-2016_05
Patent number
US09339527B2

Reaction notes

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