Sodium borohydride → 3-Amino-3-(3,4-dimethoxyphenyl)propan-1-ol

To a stirred solid of sodium borohydride (94.18 grams, 2.49 mol) at 0° C., was added methanol (50 mL). To this mixture at 0° C. was added a solution of methyl 3-amino-3-(3',4'-dimethoxyphenyl)propionate (59.5 grams, 249 mmol) in methanol (950 mL) over 1 hour. The mixture was stirred in that ice-water bath until the temperature of the reaction mixture stayed at 35° C. or lower for 30 minutes. (Caution: If the ice-water bath was removed too early, a highly exothermic reaction may occur.) The water bath was then removed and the solution was refluxed for 16 hours. The solution was allowed to cool to room temperature. To the solution was added water (300 mL), followed by methylene chloride (250 mL) at 0° C. The resulting suspension was filtered. Half of the filtrate was removed in vacuo. The resulting solution was dissolved in methylene chloride (500 mL) and water (300 mL). The organic layer was separated. The aqueous layer was extracted with methylene chloride (3×500 mL). The combined organic layers were washed with brine (100 mL), and dried over magnesium sulfate. Removal of solvent gave an oil. The resulting oil was dried in vacuo to afford 3-amino-3-(3',4'-dimethoxyphenyl)-1-propanol as a white solid (42.15 grams, 80% yield): mp 63.5°-65.5° C.; 1H NMR (CDCl3)δ6.91-6.78(m, 3H), 4.15-4.04(m, 1H), 3.89(s, 3H), 3.88(s, 3H), 3.84-3.71(s, 2H), 2.91-2.45(m, 1H), 1.95-1.78(m, 2H); Anal Calcd for C11H17NO3 :C, 62.54; H, 8.11; N, 6.63. Found: C, 62.01; H, 7.80; N, 6.49.

1. custom(Caution: If the ice-water bath was removed too early
2. customa highly exothermic reaction
3. custom) The water bath was then removed
4. temperaturethe solution was refluxed for 16 hours
5. additionTo the solution was added water (300 mL)
6. customfollowed by methylene chloride (250 mL) at 0° C
7. filtrationThe resulting suspension was filtered
8. customHalf of the filtrate was removed in vacuo
9. dissolutionThe resulting solution was dissolved in methylene chloride (500 mL)
10. customThe organic layer was separated
11. extractionThe aqueous layer was extracted with methylene chloride (3×500 mL)
12. washThe combined organic layers were washed with brine (100 mL)
13. dry with materialdried over magnesium sulfate
14. customRemoval of solvent
15. customgave an oil
16. customThe resulting oil was dried in vacuo

ORD record

ord-21ee0b68673c40c0b5ac3fd9aeec506d

Source dataset

uspto-grants-1997_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05703098