Hydrochloric Acid → (3S,4R)-1-ethyl-3-fluoropiperidin-4-amine dihydrochloride

A solution of N-((3S,4R)-1-ethyl-3-fluoropiperidin-4-yl)benzamide (6.58 kg, 24.16 mol) in aqueous hydrochloric acid (35 L, 209 mol) was heated to 130° C. external temperature for 10 hours then was allowed to stand overnight at room temperature. The precipitated solid was filtered off and washed with water (2 L). The filtrate was concentrated, and ethanol (20 L) was added at 60° C. The solution was slowly cooled to room temperature overnight, crystallization occurred, and the yellow suspension was cooled to 0° C. for 1 h, filtered over a glass frit, washed with chilled ethanol (10 L, 0° C.), and diethyl ether (5 L). The tan solid was removed from the filter and dried in vacuum oven to yield 4.70 kg of (3S,4R)-1-ethyl-3-fluoropiperidin-4-amine dihydrochloride (85%). 1H NMR (400 MHz, MeOD) δ 5.35 (d, J=47.2 Hz, 1H), 4.32-3.43 (m, 4H), 3.32 (s, 3H), 2.32 (s, 2H), 1.40 (s, 3H), 1.16 (d, J=6.1 Hz, 2H).

1. filtrationThe precipitated solid was filtered off
2. washwashed with water (2 L)
3. concentrationThe filtrate was concentrated
4. additionethanol (20 L) was added at 60° C
5. customcrystallization
6. temperaturethe yellow suspension was cooled to 0° C. for 1 h
7. filtrationfiltered over a glass frit
8. washwashed with chilled ethanol (10 L, 0° C.), and diethyl ether (5 L)
9. customThe tan solid was removed from the
10. filtrationfilter
11. customdried in vacuum oven

ORD record

ord-13bc27820d564c04876e44ed19234f78

Source dataset

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08461328B2