HCID 24769389, compound → N-((1R,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-yl)acetamide

Temperature

0 °C

The enamide 3 (24 g, 72 mmol) was slurried in degassed isopropanol (200 mL). The resulting slurry was transferred to the appropriate reactor. Prior to the addition of the catalyst solution, the content of the reactor was purged with nitrogen. A solution of (R,R)-MeBPE(COD)RhBF4 catalyst (20.1 mg, 0.036 mmol, 0.05 mol %) in isopropanol (IPA) (100 mL) was added to the reactor. The content was cooled to 0° C. and purged with nitrogen three times. The reactor was then purged with hydrogen and pressurized to 90 psig. The reaction was aged with agitation at 0° C. for 7.5 h and conversion was monitored by the hydrogen uptake. The content was then warmed to RT and hydrogen was vented. After purging with nitrogen, the contents were drained. The reaction mixture was heated to 50° C. and filtered through a pad of Celite. The clear orange solution was concentrated to ˜50% volume (150 mL) and diluted with toluene (5.9 g, 5 wt %). The suspension was heated to 65° C. and water (14.7 mL) was added dropwise to form a cloudy solution. The slurry was slowly cooled to −10° C. and aged for 30 minutes. The solid was filtered and washed with cold IPA (2×45 mL). The cake was dried under vacuum at 45° C. overnight to afford 20.0 g (83% yield) of trans acetamide 4 (>99% de).

1. additionPrior to the addition of the catalyst solution
2. customthe content of the reactor was purged with nitrogen
3. custompurged with nitrogen three times
4. customThe reactor was then purged with hydrogen
5. temperatureThe content was then warmed to RT
6. customAfter purging with nitrogen
7. temperatureThe reaction mixture was heated to 50° C.
8. filtrationfiltered through a pad of Celite
9. concentrationThe clear orange solution was concentrated to ˜50% volume (150 mL)
10. additiondiluted with toluene (5.9 g, 5 wt %)
11. temperatureThe suspension was heated to 65° C.
12. additionwater (14.7 mL) was added dropwise
13. customto form a cloudy solution
14. temperatureThe slurry was slowly cooled to −10° C. and aged for 30 minutes
15. filtrationThe solid was filtered
16. washwashed with cold IPA (2×45 mL)
17. customThe cake was dried under vacuum at 45° C. overnight

ORD record

ord-499793fe86e948778384ae1e28e62fb3

Source dataset

uspto-grants-2013_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08524950B2