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

HRID 1487835ノート

反応式

HRID 1487835 の反応式
[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]

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 26038Nickel(II) iodide触媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-bd4313892ac24ba59b284cb7a69e4e5d
出典データセット
uspto-grants-2016_08
特許番号
US09428502B2

反応ノート

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