Potassium Carbonate → HCID 67278856, compound

Intermediate 3, 4-bromo-1-(bromomethyl)-2-chlorobenzene (15.4 g, 55 mmol) was added to a mixture of (2R)-2-methylpyrrolidine HBr (9.0 g, 55 mmol), potassium carbonate (18 g, 130 mmol), and 150 mL of dimethylformamide under ice cooling. The mixture was allowed to reach room temperature, and the stirring was continued overnight. The mixture was evaporated. Water (400 mL) was added followed by addition of 5M NaHSO4 to attain pH˜2. The organic layer was separated. The aqueous phase was extracted with Et2O (2×200 mL). The organic layers were discarded. The aqueous fraction was alkalized with K2CO3 to pH˜12 and subjected to extraction with Et2O (2×300 mL). The organic layer was washed with brine, dried over anhydrous Na2SO4 (100 g), and evaporated in vacuo. The residue was distilled at 1 mmHg, bp 95° C. to give the title compound (12.25 g, 79%). LC/MS data: 289.9 and 287.9 (M)+ (calculated for C12H15BrClN 288.6). 1H NMR data (DMSO-d6): δ 7.66 (d, 1H, J=1.9 Hz, Ar—H); 7.52 (dd, 1H, J1=1.9 Hz, J2=8.0 Hz, Ar—H), 7.43 (d, 1H, J=8.1 Hz, Ar—H), 3.91 (d, 1H, J=14.4 Hz), 2.28 (d, 2H, J=8.5 Hz); 2.78-2.85 (m, 1H); 2.42-2.49 (m, 1H); 2.11 (dd, 1H, J1=8.8 Hz, J2=17.6 Hz); 1.87-1.97 (m, 1H); 1.57-1.67 (m, 2H); 1.27-1.39 (m, 1H); 1.08 (d, 3H, J=5.9 Hz).

1. customto reach room temperature
2. customThe mixture was evaporated
3. additionWater (400 mL) was added
4. additionfollowed by addition of 5M NaHSO4
5. customThe organic layer was separated
6. extractionThe aqueous phase was extracted with Et2O (2×200 mL)
7. extractionsubjected to extraction with Et2O (2×300 mL)
8. washThe organic layer was washed with brine
9. dry with materialdried over anhydrous Na2SO4 (100 g)
10. customevaporated in vacuo
11. distillationThe residue was distilled at 1 mmHg, bp 95° C.

ORD record

ord-28e4d6399140489b8dacf566a6a2b57e

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158673B2