Formaldehyde → 1-Boc-4-(3-Chloro-2-dimethylaminomethyl-phenyl)-piperazine

Sodium borohydride (1.2 g, 31.4 mmol) was dissolved in THF (20 mL) and TFA (2.42 mL, 31.4 mmol) in THF (20 mL) was added dropwise at 0° C., and the reaction was stirred for about 30 minutes. 1-Boc-4-(3-Chloro-2-cyano-phenyl)-piperazine (2.0 g, 6.3 mmol) was dissolved in ThF (20 mL) and added dropwise to the solution at 0° C., and the reaction was stirred for about 24 hours. The reaction was carefully quenched with H2O and ethyl acetate (200 mL) was added. The mixture was washed with H2O (3×25 mL), brine (25 mL) and dried over MgSO4. The solvents were removed in vacuo and the crude reaction mixture was dissolved into acetonitrile (7 mL). Formalin (1.6 mL, 59.2 mmol) was added, followed by sodium cyanoborohydride (0.26 g, 7.4 mmol) at 0° C. The reaction was warmed to r.t. and stirred for about one hour. The reaction was quenched with H2O and ethyl acetate (100 mL) was added. The solution was washed with saturated NaHCO3 (2×10 mL) and dried over MgSO4. Purification by silica gel chromatography (1:1 hexanes/ethyl acetate) gave the title compound as a yellow oil (180 mg, 13%).

1. additionadded dropwise to the solution at 0° C.
2. stirringthe reaction was stirred for about 24 hours
3. customThe reaction was carefully quenched with H2O and ethyl acetate (200 mL)
4. additionwas added
5. washThe mixture was washed with H2O (3×25 mL), brine (25 mL)
6. dry with materialdried over MgSO4
7. customThe solvents were removed in vacuo
8. customthe crude reaction mixture
9. stirringstirred for about one hour
10. customThe reaction was quenched with H2O and ethyl acetate (100 mL)
11. additionwas added
12. washThe solution was washed with saturated NaHCO3 (2×10 mL)
13. dry with materialdried over MgSO4
14. customPurification by silica gel chromatography (1:1 hexanes/ethyl acetate)

ORD record

ord-d0d74fc97c394b8fa390f1291a0c069e

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07291619B2