Formic Acid → (R)-N-[5-(2-Bromo-1-hydroxyethyl)-2-(phenylmethoxy)phenyl]formamide
Reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([OH:18])[CH2:16][Br:17])=[CH:11][C:10]=1[N+:19]([O-])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:22](O)=[O:23].C(OC(=O)C)(=O)C>C1COCC1.C1(C)C=CC=CC=1.O=[Pt]=O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([OH:18])[CH2:16][Br:17])=[CH:11][C:10]=1[NH:19][CH:22]=[O:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Procedure
A Parr hydrogenator was charged with PtO2 and 1-(4-benzyloxy-3-nitro-phenyl)-2-bromo-1-(R)-ethanol (4) (0.72 g, 2.04 mmol) dissolved in a mixed solvent of THF (8 mL) and toluene (8 mL). The mixture was hydrogenated at 55 psi at rt for 16 h. Then a mixture of formic acid (0.13 mL, 3.45 mmol) and acetic anhydride (0.22 mL, 2.33 mmol) was added and stirring was continued at rt for 66 h. The catalyst was filtered through a Celite pad and the filtrate was concentrated by rotary evaporation. The resulting residue was purified by Biotage silica gel column chromatography eluting with ethyl acetate/dichloromethane (gradient 0% to 10%) to give the desired formamide 5 as a white solid (0.45 g, 63%): 1H NMR (300 MHz, CDCl3) δ 2.95 (s, 1H), 3.52 (m, 1H), 3.60 (m, 1H), 4.85 (m, 1H), 5.08 (s, 2H), 6.96 (d, 1H), 7.13 (dd, 1H), 7.39 (m, 5H), 7.88 (br, 1H), 8.37 (dd, 1H).
Workup
- additionwas added
- waitwas continued at rt for 66 h
- filtrationThe catalyst was filtered through a Celite pad
- concentrationthe filtrate was concentrated by rotary evaporation
- customThe resulting residue was purified by Biotage silica gel column chromatography
- washeluting with ethyl acetate/dichloromethane (gradient 0% to 10%)
Sources & evidence
- ORD record
- ord-55a673b1fd654778915d47ade1ed16a8
- Source dataset
- uspto-grants-2012_04
- Patent number
- US08163758B2
Reaction notes
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