CID 71433830 → N-((1R,2S)-1-(3-fluorobenzyl)-7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)propionamide
Reaction equation
C[C@@H](PC)[C]1[C](P(C2C3C(=CC=CC=3)C=CC=2)C2C3C(=CC=CC=3)C=CC=2)[CH][CH][CH]1.[F:31][C:32]1[CH:33]=[C:34]([CH:53]=[CH:54][CH:55]=1)[CH2:35][C:36]1[C:45]2[C:40](=[CH:41][CH:42]=[C:43]([O:46][CH3:47])[CH:44]=2)[CH2:39][CH2:38][C:37]=1[NH:48][C:49](=[O:52])[CH2:50][CH3:51].[H][H]>[Rh+].ClC1CCCCC=CC=1.CO>[F:31][C:32]1[CH:33]=[C:34]([CH:53]=[CH:54][CH:55]=1)[CH2:35][C@@H:36]1[C:45]2[C:40](=[CH:41][CH:42]=[C:43]([O:46][CH3:47])[CH:44]=2)[CH2:39][CH2:38][C@@H:37]1[NH:48][C:49](=[O:52])[CH2:50][CH3:51]Participants
6
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 50 °C
Procedure
Chlorocyclooctadiene rhodium(I) dimer (0.165 g, 0.669 mmol of Rh), Josiphos SL-J216-2 (0.451 g, 0.702 mmol), and N-(1-(3-fluorobenzyl)-7-methoxy-3,4-dihydronaphthalen-2-yl)propionamide (45.4 g, 134 mmol) were combined in a metal reactor, and the vessel was inerted with argon. Degassed methanol (223 ml) was added, and the reactor was agitated under argon for 20 min at 50° C. The reactor was pressurized with 60 psig of hydrogen and stirred at 60° C. for 30 hrs. HPLC analysis indicated complete conversion and 95.2% ee. The mixture was concentrated, filtered in EtOAc through silica gel, concentrated, slurried in hot heptane, filtered, and dried to yield 39.6 g (yield: 87%) of the title compound.
Workup
- stirringstirred at 60° C. for 30 hrs
- concentrationThe mixture was concentrated
- filtrationfiltered in EtOAc through silica gel
- concentrationconcentrated
- filtrationfiltered
- customdried
Sources & evidence
- ORD record
- ord-7b7e2a2298e749bbbf1659ce2120ff02
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09227901B2
Reaction notes
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