4-Cyanophenylboronic acid → 1,1-Dimethylethyl 3-(4-cyanophenyl)-1-azetidinecarboxylate

HRID 1487835Notes

Reaction equation

HRID 1487835 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1)#[N:2].Cl.N[C@@H]1CCCC[C@H]1O.C[Si](C)(C)N[Si](C)(C)C.[Na].I[CH:32]1[CH2:35][N:34]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:33]1>[Ni](I)I>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:32]2[CH2:33][N:34]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:35]2)=[CH:5][CH:4]=1)#[N:2]

Participants

6

Reactant 4

HCID 27343264-Cyanophenylboronic acidHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 12228412Cyclohexanol, 2-amino-, hydrochloride (1:1), (1R,2R)-HCID 45051731Sodium hexamethyidisilazane

Product 1

HCID 109671701,1-Dimethylethyl 3-(4-cyanophenyl)-1-azetidinecarboxylate

Reagents, catalysts & solvents 1

HCID 26038Nickel(II) iodideCatalyst

Procedure

A modified procedure to that described in Org. Lett. 2008, 10, 3259 was performed as follows. To a 20-mL vial was added (4-cyanophenyl)boronic acid (1.01 g, 6.87 mmol), trans-2-aminocyclohexanol hydrochloride (32 mg, 0.21 mmol), nickel (II) iodide (66 mg, 0.21 mmol) and sodium hexamethyldisilazane (1.29 g, 7.06 mmol). The system was purged with nitrogen and charged with isopropyl alcohol (7 mL). The mixture was stirred at room temperature for 10 minutes then sonicated for 1 min. While stirring, tert-butyl 3-iodoazetidine-1-carboxylate (1.00 g, 3.53 mmol) was added and the syringe rinsed with isopropyl alcohol (2×500 μL). The suspension was stirred at 80° C. for 1 hour then concentrated under reduced pressure. The residue was purified by silica gel chromatography (hexanes to 25% ethyl acetate) to yield the title compound as a pale yellow oil which solidified upon standing (0.832 g, 46%). m/z (ES+) 203 (M-C4H8+H)+. 1H NMR (400 MHz, CDCl3): δ 7.65 (d with fine str., J=8.4 Hz, 2H), 7.43 (d with fine str., J=8.4 Hz, 2H), 4.37 (app t, J=8.8 Hz, 2H), 3.98-3.91 (m, 2H), 3.81-7.73 (m, 1H).

Workup

  1. customThe system was purged with nitrogen
  2. additioncharged with isopropyl alcohol (7 mL)
  3. customthen sonicated for 1 min
  4. stirringWhile stirring
  5. washthe syringe rinsed with isopropyl alcohol (2×500 μL)
  6. stirringThe suspension was stirred at 80° C. for 1 hour
  7. concentrationthen concentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (hexanes to 25% ethyl acetate)

Sources & evidence

ORD record
ord-bd4313892ac24ba59b284cb7a69e4e5d
Source dataset
uspto-grants-2016_08
Patent number
US09428502B2

Reaction notes

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