Sodium bis(trimethylsilyl)amide → 3-Methyl-4-(oxetan-3-YL)benzonitrile

HRID 1405392

Reaction equation

HRID 1405392 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[C:5]([CH3:12])[CH:4]=1)#[N:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].I[CH:24]1[CH2:27][O:26][CH2:25]1>C(O)(C)C.C(O)C.I[Ni]I.Cl.N[C@H]1CCCC[C@@H]1O>[CH3:12][C:5]1[CH:4]=[C:3]([CH:8]=[CH:7][C:6]=1[CH:24]1[CH2:27][O:26][CH2:25]1)[C:1]#[N:2]

Participants

8

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 133566863-IodooxetaneHCID 16218401(4-Cyano-2-methyl-phenyl)boronic acid

Product 1

HCID 681533093-Methyl-4-(oxetan-3-YL)benzonitrileYield 65.42%

Reagents, catalysts & solvents 4

HCID 26038Nickel(II) iodideCatalystHCID 11715205(1S,2S)-2-Aminocyclohexanol hydrochlorideCatalystHCID 702EthanolSolventHCID 3776IsopropanolSolvent2×

Procedure

(4-Cyano-2-methyl-phenyl)boronic acid (1.75 g, 10.87 mmol), diiodonickel (102 mg, 0.326 mmol), (1S,2S)-2-aminocyclohexan-1-ol hydrochloride (50 mg, 0.33 mmol) and NaHMDS (2.01 g, 11.0 mmol) were combined in isopropanol (10 mL) under N2 in a pressure vial. A solution of 3-iodooxetane (1.00 g, 5.44 mmol) in isopropanol (1 mL) was added. The vial was immersed in a pre-heated 90° C. oil bath and stirred for 2 h, then cooled, diluted with ethanol (20 mL), filtered over Celite, concentrated, then absorbed onto Celite and purified by silica gel column chromatography (0-60% EtOAc/hexane) to give 3-methyl-4-(oxetan-3-yl)benzonitrile (616 mg, 3.556 mmol, 65.42%) as a white solid. ESI-MS m/z calc. 173.1, found 174.3 (M+1)+; Retention time: 1.09 minutes (3 min run).

Workup

  1. customwas immersed in a pre-heated 90° C.
  2. temperaturecooled
  3. filtrationfiltered over Celite
  4. concentrationconcentrated
  5. customabsorbed onto Celite
  6. custompurified by silica gel column chromatography (0-60% EtOAc/hexane)

Sources & evidence

ORD record
ord-e1140e27dd8b4332a0632d541dab42c0
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Linked notes

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