Trifluoroacetic acid → 3-Bromo-2,5-dimethyl-4-{[4-(trifluoromethyl)phenyl]methyl}thiophene

HRID 870057Notes

Reaction equation

HRID 870057 reaction equation
[Br:1][C:2]1[C:3]([CH:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)O)=[C:4]([CH3:8])[S:5][C:6]=1[CH3:7].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>ClCCl>[Br:1][C:2]1[C:3]([CH2:9][C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:19])([F:18])[F:20])=[CH:15][CH:16]=2)=[C:4]([CH3:8])[S:5][C:6]=1[CH3:7]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 45140400HCID 45140400, compound

Product 1

HCID 451405883-Bromo-2,5-dimethyl-4-{[4-(trifluoromethyl)phenyl]methyl}thiophene

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (4-bromo-2,5-dimethyl-3-thienyl)[4-(trifluoromethyl)phenyl]methanol (74.0 g, 200 mmol) Example 11, Step 2 and triethylsilane (130 mL, 800 mmol) in 500 mL of dichloromethane at 0° C. under nitrogen is added trifluoroacetic acid (155 mL, 2.00 mol) such as to maintain an internal temperature between 1 and 4.5° C. Most of the volatiles are removed under reduced pressure and the resulting solution poured onto ether (1 L) and a mixture of sat. aq. sodium bicarbonate and water (500 mL). The phases are separated. The organic layer is washed with brine (200 mL), dried over magnesium sulphate and concentrated under reduced pressure. The residue is diluted and concentrated twice from toluene (300 mL). The residue is split in two equal parts, diluted with hexanes (each part with 30 mL) and each part is applied onto 330 g silica gel columns for purification with Combi Flash chromatography system (100% hexanes for 5 minutes then going to 5% ethyl acetate/95% hexanes over 21 minutes to afford the desired product as a colorless liquid.

Workup

  1. temperatureto maintain an internal temperature between 1 and 4.5° C
  2. customMost of the volatiles are removed under reduced pressure
  3. additionthe resulting solution poured onto ether (1 L)
  4. additiona mixture of sat. aq. sodium bicarbonate and water (500 mL)
  5. customThe phases are separated
  6. washThe organic layer is washed with brine (200 mL)
  7. dry with materialdried over magnesium sulphate
  8. concentrationconcentrated under reduced pressure
  9. additionThe residue is diluted
  10. concentrationconcentrated twice from toluene (300 mL)
  11. customThe residue is split in two equal parts
  12. additiondiluted with hexanes (each part with 30 mL) and each part
  13. customis applied onto 330 g silica gel columns for purification with Combi Flash chromatography system (100% hexanes for 5 minutes

Sources & evidence

ORD record
ord-99bdb2698dd747b88603487d31e7b2f4
Source dataset
uspto-grants-2015_03
Patent number
US08969394B2

Reaction notes

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