5-Diethylphosphono-2-thiophenecarboxaldehyde → 3-{[5-(Diethoxy-phosphoryl)-thiophen-2-yl]-hydroxy-methyl}-5-isopropoxy-benzoic acid
Reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][CH:12]([CH3:14])[CH3:13])[CH:10]=1)[C:5]([OH:7])=[O:6].[Li]CCCC.[CH2:20]([O:22][P:23]([C:28]1[S:29][C:30]([CH:33]=[O:34])=[CH:31][CH:32]=1)(=[O:27])[O:24][CH2:25][CH3:26])[CH3:21]>C1COCC1>[CH2:20]([O:22][P:23]([C:28]1[S:29][C:30]([CH:33]([OH:34])[C:2]2[CH:3]=[C:4]([CH:8]=[C:9]([O:11][CH:12]([CH3:14])[CH3:13])[CH:10]=2)[C:5]([OH:7])=[O:6])=[CH:31][CH:32]=1)([O:24][CH2:25][CH3:26])=[O:27])[CH3:21]Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 3-bromo-5-isopropoxy-benzoic acid (2.0 g, 8.26 mmol) in THF (30 ml) was added 1.6 M nBuLi (10.6 ml, 16.94 mmol) at −78° C. The reaction was stirred at −78° C. for 1 h and treated with a solution of (5-formyl-thiophen-2-yl)-phosphonic acid diethyl ester (2.5 g, 9.91 mmol) in THF. After stirring at −78° C. for 30 min, the reaction mixture was warmed up to r.t. and quenched by water, diluted with EtOAc. The aqueous layer was separated, acidified with 2N HCl to pH<1, and extracted with EtOAc (3×). The combined EtOAc layers were dried over MgSO4, filtrated, concentrated to give the crude product 3-{[5-(diethoxy-phosphoryl)-thiophen-2-yl]-hydroxy-methyl}-5-isopropoxy-benzoic acid.
Workup
- stirringAfter stirring at −78° C. for 30 min
- temperaturethe reaction mixture was warmed up to r.t.
- customquenched by water
- additiondiluted with EtOAc
- customThe aqueous layer was separated
- extractionextracted with EtOAc (3×)
- dry with materialThe combined EtOAc layers were dried over MgSO4
- filtrationfiltrated
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-180298702bf340e8bdb7da94082b2188
- Source dataset
- uspto-grants-2015_01
- Patent number
- US08940927B2
Reaction notes
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