Proton sponge → tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-methoxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate

HRID 75753노트

반응식

HRID 75753 반응식
[CH2:1]([C@@H:8]1[C@@H:16]([O:17][CH2:18][CH2:19][CH:20]([OH:22])[CH3:21])[C@H:15]([CH3:23])[O:14][C:13](=[O:24])[C@@H:12]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:33]N(C1C2C(N(C)C)=CC=CC=2C=CC=1)C.F[B-](F)(F)F.C[O+](C)C.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:1]([C@@H:8]1[C@@H:16]([O:17][CH2:18][CH2:19][CH:20]([O:22][CH3:33])[CH3:21])[C@H:15]([CH3:23])[O:14][C:13](=[O:24])[C@@H:12]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:30])([CH3:29])[CH3:31])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 4

HCID 88675Proton spongeHCID 516892Sodium BicarbonateHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 86701247tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-hydroxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate

생성물 1

HCID 86701248tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-methoxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate수율 84.7%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-hydroxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate (82 mg, 0.18 mmol, 1.00 equiv) in CH2Cl2 (1.8 mL) were added proton sponge (156 mg, 0.726 mmol, 4.00 equiv) and trimethyloxonium tetrafluoroborate (54 mg, 0.36 mmol, 2.0 equiv). The resulting suspension was stirred at room temperature for 1 h, poured into ½ sat'd NaHCO3 solution (20 mL), and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated to provide a yellow oil. Purification by automated silica gel column chromatography (1-6% acetone in CH2Cl2) provided tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-methoxybutoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate (71 mg, 84%) as a sticky oil: 1H NMR (400 MHz, CDCl3) δ 7.32-7.23 (m, 2H), 7.23-7.13 (m, 3H), 5.18 (d, J=6.9 Hz, 1H), 5.02-4.86 (m, 1H), 4.60 (q, J=7.2 Hz, 1H), 3.94-3.75 (m, 2H), 3.75-3.62 (m, 1H), 3.62-3.41 (m, 3H), 3.36 (dd, J=10.5, 6.5 Hz, 1H), 3.33-3.22 (m, 4H), 3.21-3.04 (m, 2H), 2.29 (t, J=12.5 Hz, 1H), 2.00-1.81 (m, 1H), 1.81-1.68 (m, 2H), 1.48 (s, 3H), 1.41 (s, 9H), 1.15 (d, J=6.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 172.21, 154.98, 139.93, 139.88, 129.13, 128.42, 126.10, 85.02, 80.03, 75.51, 75.45, 73.41, 73.39, 72.91, 72.58, 69.09, 68.84, 55.94, 55.89, 53.01, 47.27, 47.14, 37.41, 37.35, 35.14, 35.03, 28.27, 19.09, 18.73.

후처리

  1. extractionextracted with CH2Cl2 (3×20 mL)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto provide a yellow oil
  6. customPurification by automated silica gel column chromatography (1-6% acetone in CH2Cl2)

출처 및 근거

ORD 기록
ord-a044963bb99e4eb4bbbfc89de16eac62
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08835462B2

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