Potassium bis(trimethylsilyl)amide → 4-(4-Cyano-3-methylphenyl)tetrahydro-2H-thiopyran-4-carbonitrile

HRID 419952

Reaction equation

[S:1]1[CH2:6][CH2:5][CH:4]([C:7]#[N:8])[CH2:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].F[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[C:22]([CH3:28])[CH:21]=1>C1COCC1>[C:24]([C:23]1[CH:26]=[CH:27][C:20]([C:4]2([C:7]#[N:8])[CH2:5][CH2:6][S:1][CH2:2][CH2:3]2)=[CH:21][C:22]=1[CH3:28])#[N:25]

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of tetrahydro-2H-thiopyran-4-carbonitrile (197 mg, 1.55 mmol) and THF (2.0 mL) is slowly added via syringe to a mixture of KHMDS (324 mg, 1.63 mmol) in THF (3.0 mL), stirring at −78° C. under nitrogen. The temperature is maintained at −78° C. for 30 min. before a mixture of 4-fluoro-2-methylbenzonitrile (222 mg, 1.64 mmol) in THF (1.0 mL) is slowly added to the vessel. The mixture is allowed to warm to room temperature and is stirred for 3 hours before being quenched with saturated aqueous NH4Cl. The solvent is removed by rotary evaporator and EtOAc (10.0 mL) and water (10.0 mL) are added. The phases are partitioned and the organic is washed with brine, dried with Na2SO4 and concentrated to yield the product (252 mg, 1.04 mmol, 67%). 1H NMR (400 MHz, DMSO-D6) δ ppm 1.84-1.95 (m, 2H), 2.03-2.14 (m, 2H), 2.51 (s, 3H), 2.57-2.72 (m, 4H), 7.23-7.31 (m, 1H), 7.41 (dd, J=9.96, 1.76 Hz, 1H), 7.89 (dd, J=8.59, 5.86 Hz, 1H).

Workup

additionis slowly added to the vessel
temperatureto warm to room temperature
stirringis stirred for 3 hours
custombefore being quenched with saturated aqueous NH4Cl
customThe solvent is removed by rotary evaporator and EtOAc (10.0 mL) and water (10.0 mL)
additionare added
customThe phases are partitioned
washthe organic is washed with brine
dry with materialdried with Na2SO4
concentrationconcentrated

Sources & evidence

ORD record: ord-294cf2cad1814cd8b0ac3b130c83bbff
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08093402B2

Linked notes

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