Trifluoroacetic acid → Methyl 4-((3-formylpyrrolidin-1-yl)methyl)benzoate

Tert-Butyl 3-formylpyrrolidine-1-carboxylate (4.75 g, 23.84 mmol) was dissolved in dichloromethane (DCM) (20 mL). Trifluoroacetic acid (15 mL, 195 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour. After concentrating acetonitrile (100 mL) was added followed by methyl 4-(bromomethyl)benzoate (6.55 g, 28.6 mmol) and potassium carbonate (16.47 g, 119 mmol). The reaction was heated to reflux for 16 hours. The mixture was filtered and concentrated. Dichloromethane (75 ml) was added and the solution was washed with water, dried over MgSO4, filtered and concentrated. The residue was purified via silica gel chromotography (0% to 100% EtOAc:Hex; 50 g-HP-silica gel column). Obtained 2.00 g 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.99-2.23 (m, 2H), 2.46-2.57 (m, 1H), 2.60-2.79 (m, 2H), 2.88-2.99 (m, 2H), 3.68 (d, J=4.29 Hz, 2H), 3.92 (s, 3H), 7.40 (d, J=8.59 Hz, 2H), 7.93-8.09 (m, 2H), 9.66 (d, J=2.02 Hz, 1H);

1. concentrationAfter concentrating acetonitrile (100 mL)
2. additionwas added
3. temperatureThe reaction was heated
4. temperatureto reflux for 16 hours
5. filtrationThe mixture was filtered
6. concentrationconcentrated
7. additionDichloromethane (75 ml) was added
8. washthe solution was washed with water
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe residue was purified via silica gel chromotography (0% to 100% EtOAc:Hex; 50 g-HP-silica gel column)
13. customObtained 2.00 g 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.99-2.23 (m, 2H), 2.46-2.57 (m, 1H), 2.60-2.79 (m, 2H), 2.88-2.99 (m, 2H), 3.68 (d, J=4.29 Hz, 2H), 3.92 (s, 3H), 7.40 (d, J=8.59 Hz, 2H), 7.93-8.09 (m, 2H), 9.66 (d, J=2.02 Hz, 1H)

ORD record

ord-b2f175b161c14a34bab365342b75ed44

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853408B2