2,3-Dichlorobenzaldehyde → HCID 86609364, compound

To a solution of 1,1-dimethylethyl (3S)-3-(2-methylpropyl amino)-pyrrolidine-1-carboxylate (see Example 197(a)) (0.363 g, 1.5 mmol) in 1,2-dichloroethane (10 mL) was added 2,3-dichloro-benzaldehyde (1.05 g, 6.0 mmol), followed by sodium triacetoxyborohydride (0.95 g, 4.5 mmol), and the mixture left to stir for 16 h. The reaction mixture was quenched with water (5 mL) and 2N sodium hydroxide (5 mL), and the organic layer separated by passing through a hydrophobic frit. The organic solution was diluted with methanol (5 mL) and absorbed onto an Isolute™ SCX-2 ion exchange cartridge (5 g), washed with methanol (15 mL) and the product eluted with 2M ammonia in methanol solution (15 mL). The solvent was removed in vacuo to give 1,1-dimethylethyl (3S)-3-{[(2,3-dichlorophenyl)methyl](2-methylpropyl)amino}pyrrolidine-1-carboxylate as a colourless oil. This was taken up in dichloromethane (2 mL), trifluoroacetic acid (1.4 mL, 18.3 mmol) added, and the mixture stirred at room temperature for 16 h. The solvent was removed in vacuo and the residue diluted with methanol (5 mL) and absorbed onto an Isolute™ SCX-2 ion exchange cartridge (5 g). The column was washed with methanol (15 mL) and the product eluted with 2M ammonia in methanol solution (15 mL). The solvent was removed in vacuo and the residue purified by mass guided preparative LCMS. The residue was diluted with methanol (5 mL) and again absorbed onto an Isolute™ SCX-2 ion exchange cartridge (5 g). The column was washed with methanol (15 mL), the product eluted with 2M ammonia in methanol solution (15 mL) and the solvent removed in vacuo. The desired compound product was taken up in cyclohexane (15 mL) and a hot solution of L-tartaric acid (1 equiv.) in isopropanol (1 mL) was added. The solvent was removed in vacuo and the residue taken up in 40% acetonitrile/water and freeze dried to give the tile compound as a white solid.

1. waitthe mixture left
2. customThe reaction mixture was quenched with water (5 mL) and 2N sodium hydroxide (5 mL)
3. customthe organic layer separated
4. additionThe organic solution was diluted with methanol (5 mL)
5. customabsorbed onto an Isolute™ SCX-2 ion exchange cartridge (5 g)
6. washwashed with methanol (15 mL)
7. washthe product eluted with 2M ammonia in methanol solution (15 mL)
8. customThe solvent was removed in vacuo

ORD record

ord-7f31ffb914f14098baf8eb34c0e723cb

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07619096B2