Reaction equation
C(OC(=O)[NH:10][C@H:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:20][N:21]3[CH:25]=[C:24]([CH2:26][OH:27])[C:23]([C:28]([F:31])([F:30])[F:29])=[N:22]3)[CH:17]=2)[CH2:12]1)C1C=CC=CC=1.C(O)C.Cl.[H][H]>C(Cl)Cl.O=[Si]=O.[OH-].[Pd+2].[OH-]>[NH2:10][C@H:11]1[CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:20][N:21]3[CH:25]=[C:24]([CH2:26][OH:27])[C:23]([C:28]([F:31])([F:30])[F:29])=[N:22]3)[CH:17]=2)[CH2:12]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Procedure
Palladium hydroxide (20% on carbon) (3.86 mmol, 0.542 g) was wetted in a hydrogenation vessel before addition of (R)-benzyl-5-((4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-2,3-dihydro-1H-inden-2-ylcarbamate (3.86 mmol, 1.72 g) and ethanol (50 mL) followed by aqueous 5N HCl solution (5.00 mL). The mixture was stirred under 2 bar of hydrogen for 35 min before diluting with DCM (100 mL) and filtration through a dicalite pad which was then washed with 10% MeOH/DCM (150 mL). Combined organics were concentrated and partitioned between ethylacetate and saturated sodium carbonate solution. The organic layer was concentrated to give (R)-(1-((2-amino-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazol-4-yl)methanol (0.85 g, 70.7%). 1H NMR (400 MHz, CDCl3) δ 2.65 (m, 2H) 3.15 (m, 2H) 3.83 (m, 1H) 4.61 (s, 2H) 5.24 (s, 2H) 7.06 (d, 1H) 7.11 (s, 1H) 7.19 (d, 1H) 7.38 (s, 1H).
Workup
- washwas then washed with 10% MeOH/DCM (150 mL)
- concentrationCombined organics were concentrated
- custompartitioned between ethylacetate and saturated sodium carbonate solution
- concentrationThe organic layer was concentrated
Sources & evidence
- ORD record
- ord-902b3b8a6f50436d9dfd08eebadc7e87
- Source dataset
- uspto-grants-2013_09
- Patent number
- US08536214B2
Linked notes
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