Reacción #1747830

Ecuación de reacción

LiAlH4

3-(4-methoxyphenyl)-propionic acid n-propyl amid

→

N-(3-(4-methoxyphenyl)-propyl)-N-propylamine

Disolventes

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter refluxing for 12 h the mixture
2. 2
   Otroexcess hydride was destroyed by careful addition of water (10 mL), 5% aqueous NaOH (40 mL) and water (20 mL)
3. 3
   Temperaturaallowing reflux conditions
4. 4
   FiltraciónThe hot slurry was filtered
5. 5
   Lavadothe white precipitate was washed thoroughly with ethanol
6. 6
   OtroVolatiles were evaporated
7. 7
   workup.DISSOLUTIONthe resulting oil dissolved in ethyl acetate (50 mL) what
8. 8
   Extracciónwas extracted with 0.5 N aqueous HCl (4×50 mL)
9. 9
   workup.ADDITIONby addition of 30% aqueous NaOH
10. 10
    Extracciónextracted with ethyl acetate (4×50 mL)
11. 11
    Lavadowashed with brine
12. 12
    Secadodried (MgSO4)
13. 13
    Otroevaporated to dryness
14. 14
    Otroto give an oil that
15. 15
    Otropartially crystallized in diethyl ether as the hydrochloride salt
16. 16
    OtroRecrystallization from acetone/diethyl ether
17. 17
    Otrogave white flacky crystalline material
18. 18
    OtroTotal yield (as free base)

Procedimiento

To a stirred mixture of LiAlH4 (8.0 g, 200 mmol) in tetrahydrofuran (100 mL) was added dropwise a solution of 3-(4-methoxyphenyl)-propionic acid n-propyl amid (10.7 g, 49 mmol) (from a) above) in tetrahydrofuran (100 mL). After refluxing for 12 h the mixture was cooled to 50° C. and excess hydride was destroyed by careful addition of water (10 mL), 5% aqueous NaOH (40 mL) and water (20 mL) allowing reflux conditions. The hot slurry was filtered and the white precipitate was washed thoroughly with ethanol. Volatiles were evaporated and the resulting oil dissolved in ethyl acetate (50 mL) what was extracted with 0.5 N aqueous HCl (4×50 mL). The acidic phase was made alkaline (pH=9) by addition of 30% aqueous NaOH and extracted with ethyl acetate (4×50 mL). The organic layers were combined, washed with brine, dried (MgSO4) and evaporated to dryness to give an oil that partially crystallized in diethyl ether as the hydrochloride salt. Recrystallization from acetone/diethyl ether gave white flacky crystalline material. Total yield (as free base): 9.9 g, 48 mmol, 98%, mp 176-177° C. IR (neat) cm−1 2960, 2772, 1611, 1514; 1H-NMR (CDCl3) δ 9.46 (br s, 1H), 7.16 (d, 2H), 6.90 (d, 2H), 3.72 (s, 3H), 2.82 (br s, 4H), 2.59 (t, 2H), 2.15 (p, 2H), 1.83 (h, 2H), 0.89 (t, 3H) ppm; 13C-NMR (CDCl3) δ 156.6, 130.3, 127.7, 112.4, 53.7, 47.9, 45.66, 30.3, 25.9, 17.8, 9.7 ppm; MS (EI) m/z 207 (M+).

Fuente