Diisobutylaluminum hydride → [5-(3-Oxo-propyl)-tricyclo[8.2.1.03,8]trideca-3(8),4,6-trien-13-yl]-carbamic acid tert-butyl ester

HRID 722145노트

반응식

HRID 722145 반응식
CC(C[AlH]CC(C)C)C.C[O:11][C:12](=O)[CH2:13][CH2:14][C:15]1[CH:26]=[CH:25][C:24]2[CH2:23][CH:22]3[CH:27]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH:19]([CH2:20][CH2:21]3)[CH2:18][C:17]=2[CH:16]=1>C1(C)C=CC=CC=1>[C:32]([O:31][C:29](=[O:30])[NH:28][CH:27]1[CH:22]2[CH2:21][CH2:20][CH:19]1[CH2:18][C:17]1[CH:16]=[C:15]([CH2:14][CH2:13][CH:12]=[O:11])[CH:26]=[CH:25][C:24]=1[CH2:23]2)([CH3:35])([CH3:33])[CH3:34]

참가 물질

4

반응물 2

HCID 14487Diisobutylaluminum hydride3회HCID 696664593-(13-tert-Butoxycarbonylamino-tricyclo-[8.2.1.03,8]trideca-3(8),4,6-trien-5-yl)-propionic acid methyl ester

생성물 1

HCID 86591377[5-(3-Oxo-propyl)-tricyclo[8.2.1.03,8]trideca-3(8),4,6-trien-13-yl]-carbamic acid tert-butyl ester수율 56%

시약·촉매·용매 1

HCID 1140Toluene용매

반응 조건

온도
-78 °C

실험 절차

DIBAL-H (1M in toluene, 855 μl, 0.855 mmol) was added dropwise to a stirred solution of the product of Step 1 (290 mg, 0.777 mmol) in toluene (8 ml) maintaining the reaction temperature below −70° C. After stirring at −78° C. for 2 hours, more DIBAL-H (77 μl) was added and stirring was continued for 2 additional hours at −78° C. The mixture was quenched with methanol at −78° C., allowed to warm to room temperature and dispersed between ethyl acetate and 1N HCl. The organic phase was washed with sodium bicarbonate solution (sat), brine, dried and concentrated to give a colourless oil. Analysis by NMR showed ˜15% starting ester present, so the product was subjected to a further treatment with DIBAL-H (122 μl) for 2 hours at −78° C. as described above. The crude product was purified by column chromatography on silica gel eluting with 5:1 isohexane-ethyl acetate to give a colourless oil 149 mg (56%).1 NMR (CDCl3, 360 MHz) δ 9.81 (1H, s), 7.00 (1H, m), 6.90 (2H, m), 4.97 (1H, m), 4.04 (1H, m), 2.86–3.03 (4H, m), 2.75 (2H, m), 2.45–2.63 (4H, m), 1.71 (2H, m), 1.47 (9H, s), 1.19 (2H, m).

후처리

  1. temperaturemaintaining the reaction temperature below −70° C
  2. stirringstirring
  3. customwas continued for 2 additional hours at −78° C
  4. customThe mixture was quenched with methanol at −78° C.
  5. temperatureto warm to room temperature
  6. additiondispersed between ethyl acetate and 1N HCl
  7. washThe organic phase was washed with sodium bicarbonate solution (sat), brine
  8. customdried
  9. concentrationconcentrated
  10. customto give a colourless oil
  11. customThe crude product was purified by column chromatography on silica gel eluting with 5:1 isohexane-ethyl acetate

출처 및 근거

ORD 기록
ord-3f91ba4db35f41e69fb2d627395ede17
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07138400B2

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