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

HRID 879125

반응식

HRID 879125 반응식
[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

참가 물질

7

반응물 4

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

생성물 1

HCID 706553403-(3,5-Difluorophenyl)oxetane수율 63%

시약·촉매·용매 2

HCID 26038Nickel(II) iodide촉매HCID 3776Isopropanol용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-5fff55f5267347898872fca132546489
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987457B2

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