(R)-tert-butyl 3-(3-(benzyloxy)phenyl)-3-hydroxypropylcarbamate → (R)-tert-butyl 3-hydroxy-3-(3-hydroxyphenyl)propylcarbamate
Reaction equation
C([O:8][C:9]1[CH:10]=[C:11]([C@H:15]([OH:26])[CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1>CCO.[Pd]>[OH:26][C@@H:15]([C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([OH:8])[CH:10]=1)[CH2:16][CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22]Participants
Reactant 1
Product 1
Reagents, catalysts & solvents 2
Procedure
A solution of carbamate (6) (41.0 g, 115 mmol) in EtOH (500 mL) was degassed by applying vacuum once. Pd/C (10% wt, 20.0 g) was added and the mixture was degassed by alternating vacuum/H2 three times. The reaction mixture was stirred under H2 pressure of 50 psi for 4 h. The reaction mixture was filtered through Celite, the filtrate was concentrated in vacuum and the residue was purified by crystallization (10% EtOAc in hexane) to give (R)-tert-butyl 3-hydroxy-3-(3-hydroxyphenyl)propylcarbamate (Intermediate I) as a white solid. Yield (24.0 g, 78%); 1H NMR (400 MHz, DMSO-d6) δ 9.25 (s, 1H), 7.07 (t, J=7.6 Hz, 1H), 6.75-6.69 (m, 3H), 6.59 (d, J=8.0 Hz, 1H), 5.11 (d, J=4.0 Hz, 1H), 4.46-4.42 (m, 1H), 2.96 (t, J=6.8 Hz, 2H), 1.66-1.61 (m, 2H), 1.36 (s, 9H); RP-HPLC: tR=1.51 min, 98.13% (AUC); ESI MS m/z 266.28[M−H]+; Chiral HPLC 97.5% (R)-isomer.
Workup
- customthe mixture was degassed
- filtrationThe reaction mixture was filtered through Celite
- concentrationthe filtrate was concentrated in vacuum
- customthe residue was purified by crystallization (10% EtOAc in hexane)
Sources & evidence
- ORD record
- ord-341a06f519594b868534ad41b32d182e
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133154B2
Reaction notes
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