Methyl iodide → Methyl 5-(4-hydroxybutyl)thiophene-2-carboxylate
Reaction equation
[O:1]=[CH:2][CH2:3][CH2:4][CH2:5][C:6]1[S:10][C:9]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:7]=1.C([N-]C(C)C)(C)C.[Li+].O1CCCCC1OCCCI.CI.C(=O)([O-])[O-].[K+].[K+]>>[OH:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[S:10][C:9]([C:11]([O:13][CH3:14])=[O:12])=[CH:8][CH:7]=1Participants
Procedure
A synthetic scheme that is particularly useful for preparation of aldehydes of formula III where n is 3 or 4 and A is 2,5-thienylene or 2,5-furylene is illustrated by the method of synthesis of methyl 5-(4-oxobutyl)thiophene-2-carboxylate (XXII): ##STR36## an aldehyde of formula II where A is 2,5-thienylene, n is 3, and R8 is methyl. Here, the dianion prepared by the action of lithium diisopropylamide on 5-methylthiophene-2-carboxylic acid is alkylated with 3-(tetrahydro-2H-pyran-2-yloxy)propyl iodide. The product of alkylation is esterified with methyl iodide and potassium carbonate and the THP protecting group removed by acid-catalyzed hydrolysis to give methyl 5-(4-hydroxybutyl)thiophene-2-carboxylate. Oxidation of the primary alcohol functional group with chromium trioxide affords the aldehyde intermediate XXII.
Workup
- customremoved by acid-catalyzed hydrolysis
Sources & evidence
- ORD record
- ord-99ca2a7ae18e4f848b27422446727e07
- Source dataset
- uspto-grants-1980_09
- Patent number
- US04225609
Reaction notes
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