Thiophene → HCID 58188812, compound

HRID 1625117Notes

Reaction equation

HRID 1625117 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[C:6]([C:9]2[N:13]([CH2:14][CH2:15][C:16]([N:18]([CH3:20])[CH3:19])=[O:17])[N:12]=[C:11]([NH:21][C:22]3[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[C:24]([F:32])[CH:23]=3)[CH:10]=2)[CH:5]=[CH:4][N:3]=1.CCN(CC)CC.S1C=CC=C1>C1COCC1.[Ni]>[F:32][C:24]1[CH:23]=[C:22]([NH:21][C:11]2[CH:10]=[C:9]([C:6]3[CH:5]=[CH:4][N:3]=[CH:2][C:7]=3[CH3:8])[N:13]([CH2:14][CH2:15][C:16]([N:18]([CH3:20])[CH3:19])=[O:17])[N:12]=2)[CH:27]=[C:26]([C:28]([F:29])([F:31])[F:30])[CH:25]=1

Participants

6

Reactant 3

HCID 8030ThiopheneHCID 8471TriethylamineHCID 58188811HCID 58188811, compound

Product 1

HCID 58188812HCID 58188812, compoundYield 67.55%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 8028TetrahydrofuranSolvent

Procedure

E1 (0.40 g; 0.85 mmol) was dissolved in THF (50 ml) and then Et3N (0.5 ml), 10%, RaNi (0.1 g) and thiophene solution (0.1 ml) were added. The reaction mixture was stirred under H2 pressure overnight. The solvent was evaporated in vacuo and then H2O (10 ml) was added. The water phase was extracted by EtOAc (3×30 ml), the combined organic layers were washed by brine, dried (MgSO4), filtered and the solvent was evaporated in vacuo. The residue was purified by reversed-phase high-performance liquid chromatography (Shandon Hyperprep® C18 BDS (Base Deactivated Silica) 8 μm, 250 g, I.D. 5 cm). A gradient with 2 mobile phases was applied. Phase A: a 0.25% NH4HCO3 solution in water; phase B: CH3CN). The fractions were collected and worked-up. The desired fraction yielded 0.25 g of E9 (67.55%).

Workup

  1. customThe solvent was evaporated in vacuo
  2. additionH2O (10 ml) was added
  3. extractionThe water phase was extracted by EtOAc (3×30 ml)
  4. washthe combined organic layers were washed by brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was evaporated in vacuo
  8. customThe residue was purified by reversed-phase high-performance liquid chromatography (Shandon Hyperprep® C18 BDS (Base Deactivated Silica) 8 μm, 250 g, I.D. 5 cm)
  9. customThe fractions were collected

Sources & evidence

ORD record
ord-ca3f1366426d44469a4f3e32bd99a3cf
Source dataset
uspto-grants-2014_07
Patent number
US08779158B2

Reaction notes

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