Reaction #531865

Reaction equation

HCl

4-[2-(3-chlorophenyl)acetylamino]butyric acid ethyl ester

3-chlorophenylacetic acid

ethyl 4-aminobutyrate hydrochloride

EDCI

→

4-[2-(3-chlorophenyl)acetylamino]butyric acid

Yield 80.0%

Solvents

dichloromethane

Conditions

Workup

1. 1
   workup.STIRRINGThe reaction was stirred for 12 h
2. 2
   Extractionwas extracted with ether (30 mL)
3. 3
   WashThe ether solution was washed with water (50 mL)
4. 4
   Dryingdried over Na2SO4
5. 5
   Concentrationconcentrated
6. 6
   workup.DISSOLUTIONTo the residue dissolved in ethanol (10 mL)
7. 7
   workup.ADDITIONwas added 1 N aqueous NaOH solution (6 mL)
8. 8
   workup.STIRRINGafter 12 h of stirring at room temperature
9. 9
   Extractionthe product was extracted with dichloromethane (30 mL)
10. 10
    WashThe organic solution was washed with water (30 mL)
11. 11
    Dryingdried over Na2SO4
12. 12
    Concentrationconcentrated

Procedure

To a solution of 3-chlorophenylacetic acid (0.5 g, 2.93 mmol) and DMAP (0.36 g, 2.93 mmol) in dichloromethane (30 mL) was added ethyl 4-aminobutyrate hydrochloride (0.49 g, 2.93 mmol) at room temperature. After stirring for 10 min, EDCI (0.56 g, 2.93 mmol) was added portionwise to the mixture at room temperature. The reaction was stirred for 12 h. A 1 N aqueous HCl solution (20 mL) was poured into the reaction mixture, and 4-[2-(3-chlorophenyl)acetylamino]butyric acid ethyl ester was extracted with ether (30 mL). The ether solution was washed with water (50 mL), dried over Na2SO4, and concentrated. To the residue dissolved in ethanol (10 mL) was added 1 N aqueous NaOH solution (6 mL), and after 12 h of stirring at room temperature, the product was extracted with dichloromethane (30 mL). The organic solution was washed with water (30 mL), dried over Na2SO4, and concentrated to give 4-[2-(3-chlorophenyl)acetylamino]butyric acid (0.6 g, 80%). A mixture of this acid (0.6 g, 2.35 mmol), K2CO3 (0.49 g, 3.52 mmol), and 1-bromopentane (0.53 g, 3.52 mmol) in DMF (20 mL) was stirred overnight at room temperature. The product was extracted with ether (40 mL), and the ether solution was washed with water (50 mL), dried over Na2SO4, and concentrated. The residue was purified using silica gel column chromatography (hexane:ethyl acetate=3:1) to afford 988 as an oil (0.74 g, 97%): 1H NMR (CDCl3) 0.91 (3H, t, J=6.9 Hz), 1.26-1.33 (4H, m), 1.59-1.63 (2H, m), 1.80 (2H, quint, J=6.9 Hz), 2.31 (2H, t, J=6.9 Hz), 3.27 (2H, q, J=6.9 Hz), 3.52 (2H, s), 4.04 (2H, t, J=6.9 Hz), 5.72 (1H, s), 7.13-7.17 (2H, m), 7.27-7.30 (2H, m); LC-MS (ESI) m/z calcd for C17H24ClNO3 [M+H]+ 326.14. found [M+H]+ 326.15. Anal. (C17H24ClNO3) C, H, N.

Source