Methanol → HCID 178525566, compound

HRID 1422950Notes

Reaction equation

HRID 1422950 reaction equation
FC(F)(F)C(O)=O.C(O[C:13]([NH:15][C@H:16]1[CH2:21][CH2:20][C@H:19]([CH2:22][C:23]([OH:25])=[O:24])[CH2:18][CH2:17]1)=[O:14])(C)(C)C.C1(=O)O[C:29](=[O:30])[C:28]2=[CH:32][CH:33]=[CH:34][CH:35]=[C:27]12.CO>ClCCl>[O:30]=[C:29]1[C:28]2[C:27](=[CH:35][CH:34]=[CH:33][CH:32]=2)[C:13](=[O:14])[N:15]1[C@H:16]1[CH2:17][CH2:18][C@H:19]([CH2:22][C:23]([OH:25])=[O:24])[CH2:20][CH2:21]1

Participants

6

Reactant 4

HCID 887MethanolHCID 6422Trifluoroacetic acidHCID 6811Phthalic AnhydrideHCID 178453927HCID 178453927, compound

Product 1

HCID 178525566HCID 178525566, compoundYield 86.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Trifluoroacetic acid (44.6 mL, 583.0 mmol, 30.0 eq) is added at room temperature to a stirred solution of (trans-4-tert-butoxycarbonylamino-cyclohexyl)-acetic acid (5.0 g, 19.4 mmol, 1.0 eq) in dichloromethane (50 mL). After 3 hours stirring at room temperature, the reaction mixture is concentrated, the resulting residue is dissolved in pyridine (150 mL) and phthalic anhydride (5.0 g, 33.0 mmol, 1.7 eq) is added at room temperature. The reaction mixture is heated to reflux for 4 hours, pyridine is then removed and acetic anhydride (40 mL) is added. The resulting mixture is heated to reflux for 3 hours, then extracted with ethyl acetate (3×200 mL) and water (200 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: dichloromethane:methanol, 50:1 to 10:1, v/v) to afford [trans-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-cyclohexyl]-acetic acid as a white solid (4.82 g, 86% yield).

Workup

  1. concentrationthe reaction mixture is concentrated
  2. dissolutionthe resulting residue is dissolved in pyridine (150 mL)
  3. temperatureThe reaction mixture is heated
  4. temperatureto reflux for 4 hours
  5. custompyridine is then removed
  6. additionacetic anhydride (40 mL) is added
  7. temperatureThe resulting mixture is heated
  8. temperatureto reflux for 3 hours
  9. extractionextracted with ethyl acetate (3×200 mL) and water (200 mL)
  10. dry with materialThe combined organic layers are dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a residue that
  14. customis purified by column chromatography (silica gel, eluent

Sources & evidence

ORD record
ord-a6f30e8ed89e40f5861625ebd20d9311
Source dataset
uspto-grants-2015_01
Patent number
US08927541B2

Reaction notes

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