1-Propanol → 121289-95-0

Temperature

-78 °C

To a solution of propan-1-ol (6.25 mL, 83.2 mmol) and 2,6-dimethylpyridine (11.6 mL, 99.8 mmol) in CH2Cl2 (500 mL) under a nitrogen atmosphere at −78° C. was added dropwise trifluoromethanesulfonic anhydride (14.0 mL, 83.2 mmol). After stirring for 30 min at −78° C., a solution of O-benzylhydroxylamine (10.7 ml, 91.5 mmol) in CH2Cl2 (10 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 1 h, then warmed to room temperature, and stirred for additional 2 h. The reaction mixture was diluted with ice water (250 mL) and the organic layer was separated, washed with saturated aq. NaHCO3 (100 mL) and brine (100 mL). The aqueous layers were extracted again with EtOAc (1×200 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude material that was purified by silica gel flash column chromatography (CH2Cl2). To the fraction containing product and 2,6-dimethylpyridine was added 2 M aq KOH (100 mL), that was then washed with MTBE. The aqueous layer was then brought to a pH of ˜5 with 1 M aq HCl and then extracted with MTBE (3×50 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to afford 11.2 g (75%) of O-benzyl-N-propylhydroxylamine.

1. stirringThe resulting mixture was stirred at −78° C. for 1 h
2. temperaturewarmed to room temperature
3. stirringstirred for additional 2 h
4. customthe organic layer was separated
5. washwashed with saturated aq. NaHCO3 (100 mL) and brine (100 mL)
6. extractionThe aqueous layers were extracted again with EtOAc (1×200 mL)
7. dry with materialThe combined organic layers were dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto give the crude material that
11. customwas purified by silica gel flash column chromatography (CH2Cl2)
12. additionTo the fraction containing product and 2,6-dimethylpyridine
13. additionwas added 2 M aq KOH (100 mL), that
14. washwas then washed with MTBE
15. extractionextracted with MTBE (3×50 mL)
16. dry with materialThe combined organic layers were dried over MgSO4
17. filtrationfiltered
18. concentrationconcentrated under reduced pressure

ORD record

ord-82b333acdc2a4ea38d6116e7439d1d34

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09126940B2