Hydrochloric Acid → 4-Chloro-5-(1-hydroxy-propyl)-thiophene-2-carboxylic acid
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([OH:10])=[O:9])[S:5][C:6]=1Cl.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C([Li])(C)(C)C.[CH:26](=[O:29])[CH2:27][CH3:28].Cl>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([OH:10])=[O:9])[S:5][C:6]=1[CH:26]([OH:29])[CH2:27][CH3:28]Participants
7
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
A solution of 4,5-dichloro-thiophene-2-carboxylic acid in THF (25 mL) at −53° C. is treated with LiHMDS (2.5 mL, 1 M THF) and then cooled to −78° C. for 10 min. Tert-butyl lithium (3.2 mL, 1.7 M Pentane, 5.4 mmol) is added dropwise for 12 min., then treated with propanal (0.25 mL, 3.4 mmol). After 5 min. the reaction is warmed to rt and stirred overnight. The reaction mixture is then acidified with 1 N HCl (10 mL) and extracted with EtOAc (3×25 mL). Combined organic extracts are dried over MgSO4, filtered, and concentrated to provide crude 4-chloro-5-(1-hydroxy-propyl)-thiophene-2-carboxylic acid as a brown syrup (0.280 g), which is used in the next step without further purification.
Workup
- temperatureAfter 5 min. the reaction is warmed to rt
- extractionextracted with EtOAc (3×25 mL)
- dry with materialCombined organic extracts are dried over MgSO4
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-7ccd087b3a644f9b8d2d0438f8d6e781
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08084489B2
Reaction notes
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