Hydrochloric Acid → 1-(5-Chloro-2-methoxyphenyl)methanamine

Temperature

0 °C

To a solution of the above 2-chloro-2-methoxy-benzamide (1.0 g, 5.4 mmol) in anhydrous THF (10 mL) was added dropwise 1M BH3-THF complex (12.8 mL, 12.8 mmol) at 0° C. After 10 min. of stirring at 0° C., the reaction mixture was heated at 65° C. for 4 h. MeOH (approximately 10 mL) was then added to the cooled reaction mixture at 0° C. The reaction was warmed to room temperature and stirred for 10 min. The reaction solution was concentrated in vacuo to yield an oily product. The product was dissolved in 50% THF/MeOH (10 mL) and 4M HCl (10 mL) was added slowly to the solution. After 10 min. the mixture was partitioned between water (10 mL) and CH2Cl2 (20 mL). The aqueous layer was extracted with CH2Cl2 (10 mL) and the organic layers were discarded. The aqueous layer was basified to pH 9 with 5M NaOH solution. The solution was extracted with CH2Cl2 (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated in vacuo to afford 0.36 g (39%) of 5-chloro-2-methoxy-benzylamine as a white solid.

1. temperaturethe reaction mixture was heated at 65° C. for 4 h
2. temperatureThe reaction was warmed to room temperature
3. stirringstirred for 10 min
4. concentrationThe reaction solution was concentrated in vacuo
5. customto yield an oily product
6. customAfter 10 min. the mixture was partitioned between water (10 mL) and CH2Cl2 (20 mL)
7. extractionThe aqueous layer was extracted with CH2Cl2 (10 mL)
8. extractionThe solution was extracted with CH2Cl2 (3×20 mL)
9. washThe combined organic layers were washed with brine
10. dry with materialdried over MgSO4
11. concentrationconcentrated in vacuo

ORD record

ord-50401b0e4864457f99311404710465a0

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07601714B2