P-Anisidine → (R)-3-bromo-2-hydroxy-N-(4-methoxyphenyl)-2-methylpropanamide
Reaction equation
[Br:1][CH2:2][C@@:3]([OH:8])([CH3:7])[C:4](O)=[O:5].O=S(Cl)Cl.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=1.C(N(CC)CC)C>C1COCC1.C(OCC)(=O)C.O>[Br:1][CH2:2][C@@:3]([OH:8])([CH3:7])[C:4]([NH:21][C:18]1[CH:19]=[CH:20][C:15]([O:14][CH3:13])=[CH:16][CH:17]=1)=[O:5]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 0 °C
Procedure
(R)-3-Bromo-2-hydroxy-2-methylpropanic acid (8.54 g, 46.7 mmol) was placed in a 250 mL three-necked round-bottomed flask fitted with a stirring bar and an addition funnel, and dissolved in 100 mL anhydrous THF at room temperature. The solution was cooled to 0° C. Then, SOCl2 (7.78 g, 65.4 mmol) was added dropwise with stiffing in 3 hours. p-Anisidine (5.00 g, 40.6 mmol) and triethylamine (6.62 g, 65.4 mmol) were added to the mixture at 0° C. The reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure to give a yellow residue which was dissolved in ethyl acetate and water. The organic layer was separated, washed with saturated NaHCO3 solution and dried over anhydrous MgSO4. The solvent was removed and residue was subjected to flash column chromatography (silica gel, EtOAc/hexanes=1/1 v/v) to give a white solid product, 8.50 g, 63.2% yield.
Workup
- customfitted with a stirring bar and an addition funnel
- customThe solvent was removed under reduced pressure
- customto give a yellow residue which
- customThe organic layer was separated
- washwashed with saturated NaHCO3 solution
- dry with materialdried over anhydrous MgSO4
- customThe solvent was removed
- customto give a white solid product, 8.50 g, 63.2% yield
Sources & evidence
- ORD record
- ord-82cb8681d2b640949af8218b3c1c2938
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08637706B2
Reaction notes
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