Tetrabutylammonium Fluoride → (R)-2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenol
Reaction equation
[Si]([O:8][C:9]1[CH:10]=[C:11]([CH:23]=[CH:24][C:25]=1[Cl:26])[CH2:12][NH:13][C@@H:14]([C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=1)[CH3:15])(C(C)(C)C)(C)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1>[Cl:26][C:25]1[CH:24]=[CH:23][C:11]([CH2:12][NH:13][C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=2)[CH3:15])=[CH:10][C:9]=1[OH:8]Participants
Procedure
To a solution of (R)—N-(3-(tert-butyldimethylsilyloxy)-4-chlorobenzyl)-1-(3-chlorophenyl)ethanamine 82 (540 mg, 1316 μmol) in THF was added tetra-butylammonium fluoride (1M soln in THF, 1381 μL, 1381 μmol). The solution was stirred at room temperature under N2 for 3 h and then checked by TLC for completion. The reaction solution was concentrated and the crude material was purified by silica gel chromatography using a 5% to 60% gradient of EtOAc in hexanes as the eluant. The desired fractions were combined and concentrated to give (R)-2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenol 83 (200 mg, 91% yield) as a white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.34 (d, J=6.46 Hz, 3H) 3.50-3.61 (m, 2H) 3.77 (q, J=6.52 Hz, 1H) 6.78 (dd, J=8.22, 1.37 Hz, 1H) 6.96 (d, J=1.37 Hz, 1H) 7.20-7.29 (m, 4H) 7.34 (s, 1H). Mass spectrum: calculated for C15H15Cl2NO 296.2. found 297.3 (M++1).
Workup
- concentrationThe reaction solution was concentrated
- customthe crude material was purified by silica gel chromatography
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-5732d890271b483bbd3765f2ae6288cd
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08349831B2
Reaction notes
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