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N-Hydroxyphthalimide → [cis-2-[[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]methyl]-1-(4-methoxyphenyl)-4-oxo-3-azetidinyl]carbamic acid 1,1-dimethylethyl ester

HRID 247640
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HRID 247640 반응식
[CH3:1][C:2]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[C:11](=[O:12])[N:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[C@H:9]1[CH2:21][OH:22])([CH3:4])[CH3:3].O[N:25]1[C:29](=[O:30])[C:28]2=[CH:31][CH:32]=[CH:33][CH:34]=[C:27]2[C:26]1=[O:35].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>>[CH3:4][C:2]([O:5][C:6](=[O:23])[NH:7][C@H:8]1[C:11](=[O:12])[N:10]([C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)[C@H:9]1[CH2:21][O:22][N:25]1[C:29](=[O:30])[C:28]2[C:27](=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:26]1=[O:35])([CH3:1])[CH3:3]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 4

HCID 10665N-HydroxyphthalimideHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 13944672cis-2-Hydroxymethyl-1-(4-methoxyphenyl)-4-oxo-3-azetidinyl-carbamic acid 1,1-dimethylethyl ester

생성물 1

HCID 13944674[cis-2-[[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]methyl]-1-(4-methoxyphenyl)-4-oxo-3-azetidinyl]carbamic acid 1,1-dimethylethyl ester
수율 59.4%

실험 절차

To a mixture of cis-2-hydroxymethyl-1-(4-methoxyphenyl)-4-oxo-3-azetidinyl-carbamic acid 1,1-dimethylethyl ester (5.8 g, 18 mmol), N-hydroxyphthalimide (3.0 g, 18 mmole) and triphenylphosphine (5.7 g, 22 mmol) was added diethyl azodicarboxylate (3.7 g, 21 mmol). The reaction was allowed to stir at room temperature for 0.5 hours whereby the solvent was removed in vacuo. The reaction mixture was dissolved in methylene chloride and again the solvent evaporated to remove any residual THF. A solid precipitates and is washed with a solution of methylene chloride-diethyl ether (1:1). The filtrate is concentrated and the solid precipitate is again washed with a solution of methylene chloride-diethyl ether (1:1) and combined with the previously recovered material to afford 5.0 g of [cis-2-[[(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)oxy]methyl]-1-(4-methoxyphenyl)-4-oxo-3-azetidinyl]carbamic acid 1,1-dimethylethyl ester (59%). Another 1.9 g (22.3%) of product could be recovered after concentration of the filtrate followed by flash chromatography (ethyl acetate-hexane, 1:9): mp 188°-189° C.; IR (KBr) 3435, 2980, 1795, 1735, 1710, 1500, 1390, 1370, 1160, and 1130 cm-1 ; NMR(CDCl3) δ 1.48 (9H, s), 3.74 (3H, s), 4.40 (1H, br d, J=12 Hz), 4.52 (1H, m), 4.98 (1H, br d, J=12 Hz), 5.44 (1H, m), 6.22 (1H, d, J-9 Hz, exchangeable), 6.82 (2H, d, J=8 Hz), 7.43 (2H, d, J=8 Hz), 7.78 (4H, m).

후처리

  1. customwas removed in vacuo
  2. dissolutionThe reaction mixture was dissolved in methylene chloride
  3. customagain the solvent evaporated
  4. customto remove any residual THF
  5. customA solid precipitates
  6. washis washed with a solution of methylene chloride-diethyl ether (1:1)
  7. concentrationThe filtrate is concentrated
  8. washthe solid precipitate is again washed with a solution of methylene chloride-diethyl ether (1:1)

출처 및 근거

ORD 기록
ord-bccfc8cdb9a44e1aaccc94c472c5df93
출처 데이터셋
uspto-grants-1987_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US04709025

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