Thiophene → 2-[(4-Fluorophenyl)methyl]thiophene
Reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.CCCCCC.[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1>C1COCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd].CCOCC>[F:17][C:18]1[CH:25]=[CH:24][C:21]([CH2:22][C:2]2[S:1][CH:5]=[CH:4][CH:3]=2)=[CH:20][CH:19]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 0 °C
Procedure
A solution of thiophene (12.6 g, 0.15 mol) in a mixture of anhydrous ether (230 mL) and anhydrous THF (70 mL) was treated dropwise at 0° C. with a 2.5M solution of n-butyllithium in hexane (54.0 mL, 0.134 mol). The mixture was stirred at 0° C. for 1.5 hours and then transferred by cannula into a -78° C. solution of 4-fluorobenzylbromide (23.6 g, 0.125 mol) containing tetrakis(triphenylphosphine) palladium(O) (1.25 g) in anhydrous THF (200 mL). The reaction mixture was stirred for 17 hours at ambient temperature and then quenched with saturated aqueous NH4Cl solution (100 mL) and partitioned between ether and additional NH4Cl solution. The ether layer was dried over MgSO4, concentrated in vacuo and the residue subjected to vacuum distillation to give 19.4 g (81%) of 2-(4-fluorophenylmethyl)thiophene. b.p. 74°-83° C. at 0.6-0.7 mm of Hg.
Workup
- customtransferred by cannula into a -78° C.
- stirringThe reaction mixture was stirred for 17 hours at ambient temperature
- customquenched with saturated aqueous NH4Cl solution (100 mL)
- custompartitioned between ether and additional NH4Cl solution
- dry with materialThe ether layer was dried over MgSO4
- concentrationconcentrated in vacuo
- distillationthe residue subjected to vacuum distillation
Sources & evidence
- ORD record
- ord-b7d89ce142cd475fb533723ec20d32a1
- Source dataset
- uspto-grants-1996_04
- Patent number
- US05506261
Reaction notes
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