Sodium bis(trimethylsilyl)amide → 4-(Tetrahydro-2H-pyran-4-yl)benzonitrile

HRID 1260181Notes

Reaction equation

HRID 1260181 reaction equation
Cl.N[C@@H]1[CH2:8][CH2:7][CH2:6][CH2:5][C@H:4]1[OH:9].C[Si](C)(C)[N-][Si](C)(C)C.[Na+].[C:20]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)#[N:21].IC1CCOCC1>C(O)(C)C.[Ni](I)I>[O:9]1[CH2:8][CH2:7][CH:6]([C:25]2[CH:26]=[CH:27][C:22]([C:20]#[N:21])=[CH:23][CH:24]=2)[CH2:5][CH2:4]1

Participants

7

Reactant 4

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 27343264-Cyanophenylboronic acidHCID 27955064-iodotetrahydro-2H-pyranHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-

Product 1

HCID 666329764-(Tetrahydro-2H-pyran-4-yl)benzonitrile

Reagents, catalysts & solvents 2

HCID 26038Nickel(II) iodideCatalystHCID 3776IsopropanolSolvent

Procedure

186 mg (0.594 mmol) of nickel(II) iodide, 90 mg (0.594 mmol) of trans-2-aminocyclohexanol hydrochloride and 3.63 g (19.8 mmol) of sodium hexamethyldisilazide were added to a solution of 2.91 g (19.8 mmol) of 4-cyanophenylboronic acid [M. Nishimura et al., Tetrahedron 2002, 58 (29), 5779-5788] in 20 ml of isopropanol. The suspension thus obtained was stirred at RT under an argon atmosphere for 5 min. Then 2.1 g (9.90 mmol) of 4-iodotetrahydropyran [Heuberger et al., J. Chem. Soc. 1952, 910] were added. After the reaction mixture had been stirred at a temperature of 75° C. for 15 h, it was cooled to RT and substantially freed of inorganic salts with dichloromethane by filtration through approx. 50 g of silica gel. The crude product was purified by MPLC (silica gel, eluent: dichloromethane). 986 mg (53% of theory) of the title compound were obtained.

Workup

  1. customThe suspension thus obtained
  2. stirringAfter the reaction mixture had been stirred at a temperature of 75° C. for 15 h
  3. temperatureit was cooled to RT
  4. filtrationsubstantially freed of inorganic salts with dichloromethane by filtration through approx. 50 g of silica gel
  5. customThe crude product was purified by MPLC (silica gel, eluent: dichloromethane)

Sources & evidence

ORD record
ord-634714693c3346aaaf3b6cc97bfe5f28
Source dataset
uspto-grants-2013_06
Patent number
US08470811B2

Reaction notes

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