Reaction #1747830

Reaction equation

LiAlH4

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

→

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

Solvents

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   TemperatureAfter refluxing for 12 h the mixture
2. 2
   Otherexcess hydride was destroyed by careful addition of water (10 mL), 5% aqueous NaOH (40 mL) and water (20 mL)
3. 3
   Temperatureallowing reflux conditions
4. 4
   FiltrationThe hot slurry was filtered
5. 5
   Washthe white precipitate was washed thoroughly with ethanol
6. 6
   OtherVolatiles were evaporated
7. 7
   workup.DISSOLUTIONthe resulting oil dissolved in ethyl acetate (50 mL) what
8. 8
   Extractionwas extracted with 0.5 N aqueous HCl (4×50 mL)
9. 9
   workup.ADDITIONby addition of 30% aqueous NaOH
10. 10
    Extractionextracted with ethyl acetate (4×50 mL)
11. 11
    Washwashed with brine
12. 12
    Dryingdried (MgSO4)
13. 13
    Otherevaporated to dryness
14. 14
    Otherto give an oil that
15. 15
    Otherpartially crystallized in diethyl ether as the hydrochloride salt
16. 16
    OtherRecrystallization from acetone/diethyl ether
17. 17
    Othergave white flacky crystalline material
18. 18
    OtherTotal yield (as free base)

Procedure

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+).

Source