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2-[Hydroxy-(2-{4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enylamino}-ethyl)-phosphinoyloxy]-propionic acid ethyl ester → 2-(Hydroxy-{2-[4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enylamino]-ethyl}-phosphinoyloxy)-propionic Acid

HRID 910524
ノート
印刷プレビュー

反応式

HRID 910524 の反応式
C([O:3][C:4](=[O:39])[CH:5]([O:7][P:8]([OH:38])([CH2:10][CH2:11][NH:12][CH2:13][C:14]([CH3:37])=[CH:15][CH2:16][C:17]1[C:18]([O:30]CC[Si](C)(C)C)=[C:19]2[C:23](=[C:24]([CH3:28])[C:25]=1[O:26][CH3:27])[CH2:22][O:21][C:20]2=[O:29])=[O:9])[CH3:6])C>C(O)(C(F)(F)F)=O.C(Cl)Cl>[OH:38][P:8]([CH2:10][CH2:11][NH:12][CH2:13][C:14]([CH3:37])=[CH:15][CH2:16][C:17]1[C:18]([OH:30])=[C:19]2[C:23](=[C:24]([CH3:28])[C:25]=1[O:26][CH3:27])[CH2:22][O:21][C:20]2=[O:29])([O:7][CH:5]([CH3:6])[C:4]([OH:39])=[O:3])=[O:9]
参加物実験手順後処理出典と根拠反応ノート

参加物

3

反応物 1

HCID 765410322-[Hydroxy-(2-{4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enylamino}-ethyl)-phosphinoyloxy]-propionic acid ethyl ester

生成物 1

HCID 725636812-(Hydroxy-{2-[4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-2-methyl-but-2-enylamino]-ethyl}-phosphinoyloxy)-propionic Acid収率 57.2%

試薬・触媒・溶媒 1

HCID 21863450Trifluoroacetic acid methylene chloride溶媒

実験手順

A solution of 2-[hydroxy-(2-{4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enylamino}-ethyl)-phosphinoyloxy]-propionic acid ethyl ester (15 mg, 0.026 mmol) in 10% TFA-CH2Cl2 (1 mL) was stirred at ambient temperature for 10 minutes. The reaction was worked up by removal of the solvent. The residue was dissolved in THF (0.5 mL) and water (0.4 mL) and 1N aqueous NaOH solution (0.1 mL) was added. The solution was stirred at room temperature for 20 minutes when it was acidified with 1N aqueous HCl solution. The resulting solution was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, 0.1% TFA to provide 6.8 mg of the product as a white solid. 1H NMR (300 MHz, CDCl3) δ 1.38 (d, 3H, J=7 Hz), 1.91 (s, 3H), 2.13 (s, 3H), 2.12-2.28 (m, 2H), 3.12-3.33 (m, 2H), 3.41 (d, 2H, J=6 Hz), 3.56 (br s, 2H), 3.75 (s, 3H), 4.71-4.88 (m, 1H), 5.16 (s, 2H), 5.58-5.71 (m, 1H), 7.88 (br s, 3H), 8.60 (br s, 1H), 8.78 (br s, 1H) ppm; 31P (121.4 MHz, CDCl3) δ 22.0 ppm; MS (m/z) 458.3 [M+H]+, 480.3 [M+Na]+.

後処理

  1. customThe reaction was worked up by removal of the solvent
  2. dissolutionThe residue was dissolved in THF (0.5 mL)
  3. additionwater (0.4 mL) and 1N aqueous NaOH solution (0.1 mL) was added
  4. customThe resulting solution was purified by RP HPLC

出典と根拠

ORDレコード
ord-929f804396a4425996a0e0de1317b1b4
出典データセット
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08022083B2

反応ノート

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