Formaldehyde → (RS)-Methyl alpha-(Hydroxymethyl)-3,5-bis(trifluoromethyl)benzeneacetate
Reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[C:5]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C=O.[C:22](=O)([O-])[OH:23].[Na+].O>CS(C)=O>[OH:23][CH2:22][CH:13]([C:5]1[CH:4]=[C:3]([C:2]([F:18])([F:19])[F:1])[CH:8]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:6]=1)[C:14]([O:16][CH3:17])=[O:15]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 45 °C
Procedure
A mixture of methyl 3,5-bis(trifluoromethyl)benzeneacetate (Description 1, 10.0 g, 35 mmol), paraformaldehyde (1.15 g, 38.5 mmol) and sodium hydrogen carbonate (84 mg, 1 mmol) in dimethylsulfoxide (10 mL) was heated at 45° C. for 1 hour, cooled and water (200 mL) was added. The mixture was extracted with ether (2×200 mL) and the combined organic fractions were washed with water (4×100 mL) and brine (100 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with isohexane/EtOAc (75:25) to give the title compound as a colorless oil (2.0 g, 10%). 1H NMR (400 MHz, CDCl3) δ 2.27 (1H, t, J 7.0 Hz), 3.76 (3H, s), 3.94–3.99 (2H, m), 4.01–4.15 (1H, m), 7.77 (2H, s) and 7.83 (1H, s).
Workup
- temperaturecooled
- extractionThe mixture was extracted with ether (2×200 mL)
- washthe combined organic fractions were washed with water (4×100 mL) and brine (100 mL)
- dry with materialdried (MgSO4)
- customthe solvent was evaporated under reduced pressure
- customThe residue was purified by flash column chromatography on silica gel
- washeluting with isohexane/EtOAc (75:25)
Sources & evidence
- ORD record
- ord-76a81501475b445586fced18093d95be
- Source dataset
- uspto-grants-2006_09
- Patent number
- US07105507B2
Reaction notes
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