Methanol → HCID 21250931, compound

HRID 1940099Notes

Reaction equation

HRID 1940099 reaction equation
CO.[C:3](Cl)(=O)C.[O:7]=[C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][N:9]1[CH:17]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:18][C:19]([OH:21])=[O:20]>CCCCCC.CCOCC>[O:7]=[C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10][N:9]1[CH:17]([C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[C:24]([O:30][CH2:31][CH3:32])[CH:23]=1)[CH2:18][C:19]([O:21][CH3:3])=[O:20]

Participants

6

Reactant 3

HCID 887MethanolHCID 6367Acetyl chlorideHCID 183492403-(3-Ethoxy-4-methoxyphenyl)-3-(1-oxoisoindolinyl)propanoic acid

Product 1

HCID 21250931HCID 21250931, compoundYield 87.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent2×

Procedure

To an ice bath cooled solution of 50 mL of methanol was added acetyl chloride (7.2 mL, 100 mmol). After stirring for 10 minutes 3-(1-oxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propionic acid (6.00 g, 16.9 mmol) was added to the mixture. After 30 minutes the ice bath was removed and the reaction was monitored by HPLC (Waters radial pak phenyl 8×100 mm column, 240 mn, 1.5 mL/min, 35/65 acetonitrile/0.1% phosphoric acid). After 4 hours the reaction had reached completion. The methanol was removed in vacuo and the resulting residue was diluted with 50 mL of methylene chloride. The mixture was extracted with aqueous sodium bicarbonate (50 mL) and brine. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford a thick oil. Hexane (50 mL) and ether (5 mL) were added to the oil and the mixture stirred overnight in an open flask. An additional 25 mL of hexane were added to facilitate stirring. After 6 hours the slurry was filtered and the solid air dried and then dried in vacuo (60° C., <1 mm) to afford 5.45 g (87%) of methyl 3-(1-oxoisoindolin-2-yl)-3-(3-ethoxy-4-methoxyphenyl)propionate as a white solid: mp 78°-80° C.; 1H NMR (DMSO-d6) δ7.75-7.40 (m, 4H), 7.10-6.80 (m, 3H), 5.72 (t, J=7.8 Hz, 1H), 4.51 (d, J=17.7 Hz, 1H), 4.09 (d, J=17.7 Hz, 1H), 3.97 (m, 2H), 3.73 (s, 3H), 3.55 (s, 3H), 3.24 (m, 2H), 1.30 (m, 3H); 13C NMR (DMSO-d6) δ170.8, 166.8, 148.5, 147.9, 141.6, 132.0, 131.3, 131.2, 127.8, 123.4, 122.8, 119.3, 112.2, 111.8, 63.7, 55.4, 51.5, 51.0, 46.3, 36.2, 14.6; Anal. Calcd. for C21H23NO5. Theoretical: C, 68.28; H, 6.28; N, 3.79. Found: C, 68.13; H, 6.27; N, 3.70.

Workup

  1. additionwas added to the mixture
  2. customAfter 30 minutes the ice bath was removed
  3. customThe methanol was removed in vacuo
  4. additionthe resulting residue was diluted with 50 mL of methylene chloride
  5. extractionThe mixture was extracted with aqueous sodium bicarbonate (50 mL) and brine
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a thick oil
  10. stirringto facilitate stirring
  11. filtrationAfter 6 hours the slurry was filtered
  12. customthe solid air dried
  13. customdried in vacuo (60° C., <1 mm)

Sources & evidence

ORD record
ord-3adf03c3668e4a3f836bbf43feab72d4
Source dataset
uspto-grants-1997_12
Patent number
US05698579

Reaction notes

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