Reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[K+].[CH:11]1([C:17]#[N:18])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1.F[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1.Cl.CCOC(C)=O>C1COCC1>[C:17]([C:11]1([C:20]2[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)#[N:18]Participants
Conditions
- Temperature
- 0 °C
Procedure
Solid KHMDS (4.36 g, 22.0 mmol) is dissolved in THF (80.0 mL) and cooled to 0° C. Cyclohexanecarbonitrile (2.38 g, 22.0 mmol) is added, and the resulting solution is stirred for 40 minutes. A solution of 4-fluorobenzonitrile (1.33 g, 10.95 mmol) in THF (10.0 mL) is added, and the mixture is stirred for 2 hours at 0° C. and 10 hours at room temperature. 1N HCl (50.0 mL) is added, and the aqueous phase is extracted with EtOAc (4×50.0 mL). The combined organic phases are dried over MgSO4, filtered and concentrated on the rotovaporator. The product is purified by flash chromatography (CombiFlash), eluting with mixtures of heptanes and EtOAc (0% EtOAc to 30% EtOAc) (1.55 g, 7.38 mmol, 67%). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.23-1.38 (m, 1H) 1.52-1.68 (m, 2H) 1.68-1.78 (m, 1H) 1.78-1.93 (m, 4H) 2.00-2.11 (m, 2H) 7.75 (d, J=8.79 Hz, 2H) 7.91 (d, J=8.79 Hz, 2H).
Workup
- stirringthe mixture is stirred for 2 hours at 0° C. and 10 hours at room temperature
- extractionthe aqueous phase is extracted with EtOAc (4×50.0 mL)
- dry with materialThe combined organic phases are dried over MgSO4
- filtrationfiltered
- concentrationconcentrated on the rotovaporator
- customThe product is purified by flash chromatography (CombiFlash)
Sources & evidence
- ORD record
- ord-ef8997eeac214905953d25bead284cf6
- Source dataset
- uspto-grants-2012_01
- Patent number
- US08093402B2
Linked notes
Loading…