Benzyl Bromide → 2,3-Dimethyl-5-benzylthiophene

HRID 1954256Notes

Reaction equation

HRID 1954256 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[CH:5][C:6]=1[CH3:7].C(=O)=O.CC(C)=O.[CH2:15](Br)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1COCC1>[CH2:15]([C:4]1[S:3][C:2]([CH3:1])=[C:6]([CH3:7])[CH:5]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 342952,3-DimethylthiopheneHCID 18522661Acetone cardice

Product 1

HCID 102419632,3-Dimethyl-5-benzylthiopheneYield 77.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

At -78° C., to a stirred solution of 2,3-dimethylthiophene (5.00 g, 44.6 mmol) in THF (89.3 mL) was added dropwise 2.5M BuLi/hexanes (17.9 mL, 44.6 mmol). After the addition was complete, the dry ice/acetone bath was replaced with a water ice bath and the reaction was stirred for 0.75 h. At -78° C., to the reaction was added a solution of benzyl bromide (5.30 mL, 44.6 mmol) in THF (44.6 mL) that had been previously cooled to -78° C. After the addition was complete, the reaction was stirred for 18 h eventually warming to ambient temerature. The reaction was filtered through a silica gel pad eluting with 1% EtOAc/pet ether and the filtrate was concentrated. Purification on Biotage KP-Sil eluting with 1% EtOAc/pet ether gave 6.960 g (77%) of the title compound as an oil. 1H NMR (DMSO-d6) δ 2.01 (s, 3 H), 2.21 (s, 3 H), 3.98 (s, 2 H), 6.58 (s, 1 H), 7.18-7.37 (m, 5 H).

Workup

  1. additionAfter the addition
  2. additionAfter the addition
  3. stirringthe reaction was stirred for 18 h
  4. temperatureeventually warming to ambient temerature
  5. filtrationThe reaction was filtered through a silica gel pad
  6. washeluting with 1% EtOAc/pet ether
  7. concentrationthe filtrate was concentrated
  8. customPurification on Biotage KP-Sil
  9. washeluting with 1% EtOAc/pet ether

Sources & evidence

ORD record
ord-53839cb520fe44e2b5477c7120561f81
Source dataset
uspto-grants-2000_09
Patent number
US06121271

Reaction notes

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