Ethanol → HCID 57473824, compound

HRID 576593Notes

Reaction equation

HRID 576593 reaction equation
C([O:8][C:9]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:10]=1[C:11]#[N:12])C1C=CC=CC=1.C(O)C.Cl[Si:25]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:28])[CH3:27].N1C=CN=C1>[Pd].C(OCC)C>[F:20][C:17]([F:18])([F:19])[C:14]1[CH:15]=[CH:16][C:9]([O:8][Si:25]([CH:32]([CH3:34])[CH3:33])([CH:29]([CH3:31])[CH3:30])[CH:26]([CH3:28])[CH3:27])=[C:10]([CH:13]=1)[C:11]#[N:12]

Participants

7

Reactant 4

HCID 702EthanolHCID 795ImidazoleHCID 139400Triisopropylsilyl chlorideHCID 21544502HCID 21544502, compound

Product 1

HCID 57473824HCID 57473824, compoundYield 97.3%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 3283Diethyl EtherSolvent

Procedure

Intermediate B, Step 2: A 250-mL round bottom flask containing a magnetic stir bar was charged successively with 2-(benzyloxy)-5-(trifluoromethyl)benzonitrile (7.30 g, 26.3 mmol), ethanol (76 mL) and 10 wt % palladium on carbon (560 mg, 5.27 mmol). The resulting solution was put under a hydrogen atmosphere and stirred for 3 h. The solution was then filtered and evaporated until all ethanol was removed. The residue was redissolved in DMF (38 mL), and chlorotriisopropylsilane (9.02 mL, 42.1 mmol) and imidazole (2.87 g, 42.1 mmol) were added and stirred for 4 h. At this time the solution was diluted with diethyl ether (300 mL) and washed with brine (5×100 mL). The organic layer was dried (MgSO4) and concentrated on a rotary evaporator. The residue was purified using a 120 g silica gel cartridge and 20:1 Hex/EtOAc to 4:1 Hex/EtOAc to elute 5-(trifluoromethyl)-2-(triisopropylsilyloxy)benzonitrile (8.80 g, 25.6 mmol, 97% yield) as a colorless oil. LC/MS [M+H]-=344.19. 1H-NMR (400 MHz, CDCl3) δ=7.83 (s, 1H), 7.70 (dd, J=8.0, 3.6 Hz, 1H), 7.03 (d, J=8.0 Hz, 1H), 1.15-1.0 (m, 21H).

Workup

  1. filtrationThe solution was then filtered
  2. customevaporated until all ethanol
  3. customwas removed
  4. dissolutionThe residue was redissolved in DMF (38 mL)
  5. stirringstirred for 4 h
  6. washwashed with brine (5×100 mL)
  7. dry with materialThe organic layer was dried (MgSO4)
  8. concentrationconcentrated on a rotary evaporator
  9. customThe residue was purified

Sources & evidence

ORD record
ord-7a9814c2d6574f3b89f77dbd34dfc6b7
Source dataset
uspto-grants-2015_05
Patent number
US09040526B2

Reaction notes

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