3-Chlorobenzaldehyde → Methyl 4-((3-chlorobenzyl)amino)butanoate hydrochloride

Temperature

20 °C

To a solution of 4-amino-butyric acid methyl ester hydrochloride (30 g, 1 eq.) in 360 mL of THF were added TEA (67.7 mL, 2.5 eq.), then 3-chlorobenzaldehyde (19 mL, 0.9 eq.) and MgSO4 (35 g, 1.5 eq.). The reaction was stirred at 20° C. for 15 h under nitrogen. 360 mL of MeOH was added then the reaction was cooled to −20° C. NaBH4 (14.75 g, 2 eq.) was added portionwise. The reaction was stirred for 1 h at 0° C. The crude was partially concentrated under reduced pressure at 20° C., filtered and washed with DCM. The filtrate was washed with water and brine. The organic layer was dried over MgSO4, filtered and concentrated under reduced pressure at 20° C. The residue, in solution in 1600 mL of Et2O, was treated with 87 mL of HCl 2N in Et2O. A solid was formed, filtrated, washed with Et2O, then pentane and dried to afford 4-(3-chloro-benzylamino)-butyric acid methyl ester hydrochloride (32 g, yield=65%).

1. temperaturethe reaction was cooled to −20° C
2. stirringThe reaction was stirred for 1 h at 0° C
3. concentrationThe crude was partially concentrated under reduced pressure at 20° C.
4. filtrationfiltered
5. washwashed with DCM
6. washThe filtrate was washed with water and brine
7. dry with materialThe organic layer was dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure at 20° C
10. additionThe residue, in solution in 1600 mL of Et2O, was treated with 87 mL of HCl 2N in Et2O
11. customA solid was formed
12. filtrationfiltrated
13. washwashed with Et2O
14. dry with materialpentane and dried

ORD record

ord-8447e0516973421b80519cf907fa3dbe

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759334B2