Reacción #166134

Ecuación de reacción

4-methoxybenzyl bromide

O-allyl-N-benzylcinchonidinium bromide

toluene

KOH

→

tert-butyl 2-amino-3-(4-methoxyphenyl)-2-methylpropanoate

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe mixture was stirred for 5 min
2. 2
   Temperaturato warm
3. 3
   workup.STIRRINGwas stirred at ambient temperature for 16 h
4. 4
   LavadoThe reaction mixture was sequentially washed with water (20 mL) and brine (20 mL)
5. 5
   Otroseparated
6. 6
   workup.ADDITIONtreated with a 5-6 N HCl solution in IPA (7 mL) for 1 h at ambient temperature
7. 7
   LavadoThe reaction mixture was washed with water (20 mL)
8. 8
   OtroThe aqueous phase was separated
9. 9
   workup.ADDITIONtreated with toluene (20 mL)
10. 10
    OtroThe aqueous phase was separated
11. 11
    workup.ADDITIONtreated with a 2 N NaOH solution until basic
12. 12
    Extracciónthe product was extracted with toluene (20 mL)
13. 13
    LavadoThe toluene phase was washed with brine (20 mL)
14. 14
    Otroseparated
15. 15
    Secadodried over Na2SO4
16. 16
    FiltraciónThe solid was filtered

Procedimiento

Aldimine (2.00 g, 7.47 mmol) and O-allyl-N-benzylcinchonidinium bromide (0.38 g, 0.75 mmol, 0.10 equiv) were mixed with toluene (20 mL) at ambient temperature. The mixture was stirred for 30 min and then was cooled to 0° C. Powdered KOH (2.10 g, 37.35 mmol, 5 equiv) was added at once to convert the thin slurry into a yellow solution. The mixture was stirred for 5 min and 4-methoxybenzyl bromide (7.51 g, 37.35 mmol, 5 equiv) was added at 0 to 1° C. The solution was allowed to warm and was stirred at ambient temperature for 16 h. The reaction mixture was sequentially washed with water (20 mL) and brine (20 mL), separated, and treated with a 5-6 N HCl solution in IPA (7 mL) for 1 h at ambient temperature. The reaction mixture was washed with water (20 mL). The aqueous phase was separated and treated with toluene (20 mL). The aqueous phase was separated, treated with a 2 N NaOH solution until basic, and the product was extracted with toluene (20 mL). The toluene phase was washed with brine (20 mL), separated, and dried over Na2SO4. The solid was filtered and the solvent was stripped to dryness to afford tert-butyl 2-amino-3-(4-methoxyphenyl)-2-methylpropanoate; 1.70 g; 85.8% as a clear oil. 1H NMR (500 MHz, CDCl3): δ 7.13 (d, J=8.7 Hz, 2H, Ar), 6.81 (d, J=8.7 Hz, 2H, Ar), 3.78 (s, 3H, CH3), 3.05 (d, J=13.3 Hz, 1H, CH2), 2.71 (d, J=13.3 Hz, 1H, CH2), 1.62 (br. s, 2H, NH2), 1.45 (s, 9H, 3×CH3), 1.32 (s, 3H, CH3). 1H NMR analysis, carried out in the presence of 1.2 equiv of BINOL, resulted in 47.6% ee. Optical rotation (α25D, chloroform, c=1.38): −9.06°.

Fuente