Diethyl Ether → 5-(Diethoxymethyl)thiophene-3-carbaldehyde
Reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:7]([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10])[S:5][CH:6]=1.C[CH2:15][O:16]CC.C([Li])CCC.CN(C=O)C>CCCCCC>[CH2:9]([O:8][CH:7]([O:11][CH2:12][CH3:13])[C:4]1[S:5][CH:6]=[C:2]([CH:15]=[O:16])[CH:3]=1)[CH3:10]Participants
Conditions
- Temperature
- -78 °C
Procedure
A solution of 4-bromo-2-(diethoxymethyl)thiophene (500 mg, 0.002 mol) in ether (5 mL, 0.05 mol) was cooled at −78° C. To this solution, 2.5 M n-butyllithium in hexane (0.83 mL) was added dropwise. The reaction was stirred at −78° C. for 1 hour. To the reaction was added DMF (0.4 g, 0.006 mol) at −78° C. and the mixture was stirred for 30 minutes. The reaction was quenched with water and extracted with ethyl acetate. The combined organic layers were washed with saturated sodium chloride, dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by flash column chromatography to yield the 5-(diethoxymethyl)thiophene-3-carbaldehyde as an oil (170 mg, 42.0%). By 1H NMR two different regioisomers of aldehydes were formed and were not separated; (note: NMR shifts are for the major isomer only) 1H NMR (400 MHz, CDCl3): δ 9.85 (s, 1H), 8.05, 7.7 (s, 1H), 7.45, 7.15 (s, 1H), 5.7 (s, 1H), 3.65 (m, 2H), 1.25 (m, 2H).
Workup
- stirringthe mixture was stirred for 30 minutes
- customThe reaction was quenched with water
- extractionextracted with ethyl acetate
- washThe combined organic layers were washed with saturated sodium chloride
- dry with materialdried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customThe crude residue was purified by flash column chromatography
Sources & evidence
- ORD record
- ord-93b30386822b42fd909483bc9908ae28
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08933086B2
Reaction notes
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