1-Butanol → HCID 178450857, compound

HRID 1866351Notes

Reaction equation

HRID 1866351 reaction equation
[Na].[CH3:2][O:3][C:4](=[O:26])[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[C:22](C)=[CH:21][CH:20]=[CH:19][C:18]=3C)[CH:12]=2)[C:7]1=[O:25].[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:25])=[CH:9][CH:10]=[C:11]([O:16][CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1)[CH:12]=2)=[O:26])[CH2:27][CH2:28][CH3:29]

Participants

4

Reactant 3

HCID 2631-ButanolHCID 5360545SodiumHCID 66713069HCID 66713069, compound

Product 1

HCID 178450857HCID 178450857, compound

Procedure

0.79 g of sodium (34 mmol) were dissolved in 100 ml of n-butanol with stirring. Then the temperature was raised to 95° C. to 100° C., 5.70 g of [5-(2,6-dimethyl-phenoxy)-1,3-dioxo-1,3-dihydro-isoindol-2-yl]-acetic acid methyl ester (16.8 mmol) were added in one portion and stirring was continued at 95° C. to 100° C. for 3 h. Subsequently, the solvent was evaporated in vacuo, 25 ml of aqueous 2N HCl and 100 ml of ethyl acetate were added and the mixture was stirred vigorously for 30 min before it was filtered by suction. The organic phase was separated from the filtrate, dried over MgSO4 and was evaporated in vacuo to give a brown gum that was triturated with methanol. The resulting precipitate was filtered by suction and dried in vacuo to give 870 mg of a yellowish solid (A). The filtrate was evaporated in vacuo, dissolved in a small amount of methanol and stored overnight in a refrigerator. The resulting precipitate was filtered by suction and dried in vacuo to give 246 mg of a yellowish solid (B). A and B were pooled and purified by flash column chromatography on silica gel eluting with dichloromethane:ethyl acetate (98:2). Evaporation of the first fraction yielded 762 mg of the title compound; 1H NMR (CDCl3): δ=8.31 (bs, 1H), 8.12 (d, 1H), 7.60 (d, 1H), 7.35 (m, 1H), 7.09 (bs, 3H), 4.39 (t, 2H), 2.11 (s, 6H), 1.77 (m, 2H), 1.44 (m, 2H), 0.99 (t, 3H).

Workup

  1. temperatureThen the temperature was raised to 95° C. to 100° C.
  2. stirringstirring
  3. customSubsequently, the solvent was evaporated in vacuo, 25 ml of aqueous 2N HCl and 100 ml of ethyl acetate
  4. additionwere added
  5. stirringthe mixture was stirred vigorously for 30 min before it
  6. filtrationwas filtered by suction
  7. customThe organic phase was separated from the filtrate
  8. dry with materialdried over MgSO4
  9. customwas evaporated in vacuo
  10. customto give a brown gum that
  11. customwas triturated with methanol
  12. filtrationThe resulting precipitate was filtered by suction
  13. customdried in vacuo

Sources & evidence

ORD record
ord-802ff3673d5446f99d5bd21d83c5df3e
Source dataset
uspto-grants-2009_12
Patent number
US07629357B2

Reaction notes

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