Tetrahydrofuran → Morpholine-4-carboxamide

Temperature

65 °C

Carbonyl diimidazole (32 mg, 0.2 mmol) was added to a stirred solution of the carboxylic acid (Example 24) (40 mg, 0.066 mmol) in THF (3 mL) under nitrogen at room temperature. The solution was heated at 65° C. for 3 hr. After cooling to room temperature, morpholine (9 μL, 0.1 mmol) was added and the mixture heated at 50° C. for 18 hr. The solution was concentrated to dryness in vacuo. 5% Citric acid solution was added and the mixture extracted with ethyl acetate three times. The combined organic phase was washed with brine, dried (magnesium sulfate) and the solvent removed in vacuo. The residue was pre-absorbed on silica gel and chromatographed (0-5% methanol/methylene chloride) to give the titled morpholino amide compound (15 mg, 33%) (for spectral data see Table VII).

1. temperatureAfter cooling to room temperature
2. temperaturethe mixture heated at 50° C. for 18 hr
3. concentrationThe solution was concentrated to dryness in vacuo
4. addition5% Citric acid solution was added
5. extractionthe mixture extracted with ethyl acetate three times
6. washThe combined organic phase was washed with brine
7. dry with materialdried (magnesium sulfate)
8. customthe solvent removed in vacuo
9. customThe residue was pre-absorbed on silica gel
10. customchromatographed (0-5% methanol/methylene chloride)

ORD record

ord-002c55e163774ccf8ad7f6d6b3a380df

Source dataset

uspto-grants-1997_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05668279