(1R,2R)-2-Aminocyclohexanol → 3-(3,5-Difluorophenyl)oxetane

HRID 879125

反応式

HRID 879125 の反応式
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[C:6]([F:8])[CH:7]=1.N[C@@H]1CC[CH2:16][CH2:15][C@H:14]1[OH:19].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].IC1COC1>CC(O)C.[Ni](I)I>[F:1][C:2]1[CH:3]=[C:4]([CH:15]2[CH2:14][O:19][CH2:16]2)[CH:5]=[C:6]([F:8])[CH:7]=1

参加物

7

反応物 4

HCID 735777(1R,2R)-2-AminocyclohexanolHCID 2724254Sodium bis(trimethylsilyl)amideHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 133566863-Iodooxetane

生成物 1

HCID 706553403-(3,5-Difluorophenyl)oxetane収率 63%

試薬・触媒・溶媒 2

HCID 26038Nickel(II) iodide触媒HCID 3776Isopropanol溶媒2 回

実験手順

3,5-difluorophenylboronic acid (2.0 equiv.), (1R,2R)-2-aminocyclohexanol (0.06 equiv.), NaHMDS (2.0 equiv.), and nickel(II) iodide (0.06 equiv.) were dissolved in 2-propanol (0.35 M). The mixture was degassed with N2, stirred at rt for 10 min and then a solution of 3-iodooxetane (1.0 equiv.) in 2-Propanol (0.70 M) was added. The mixture was sealed and heated at 80° C. in the microwave for 20 min. The mixture was filtered through celite, eluting with EtOH and concentrated. The crude residue was purified by ISCO SiO2 chromatography eluting with 0-100% EtOAc in Heptanes to afford 3-(3,5-difluorophenyl)oxetane in 63% yield. 1H NMR (400 MHz, <cdcl3>) δ 6.88-6.96 (m, 2H), 6.72 (tt, J=2.20, 8.95 Hz, 1H), 5.08 (dd, J=6.26, 8.22 Hz, 2H), 4.71 (t, J=6.26 Hz, 2H), 4.14-4.24 (m, 1H).

後処理

  1. customThe mixture was degassed with N2
  2. customThe mixture was sealed
  3. temperatureheated at 80° C. in the microwave for 20 min
  4. filtrationThe mixture was filtered through celite
  5. washeluting with EtOH
  6. concentrationconcentrated
  7. customThe crude residue was purified by ISCO SiO2 chromatography
  8. washeluting with 0-100% EtOAc in Heptanes

出典と根拠

ORDレコード
ord-5fff55f5267347898872fca132546489
出典データセット
uspto-grants-2015_03
特許番号
US08987457B2

関連ノート

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