Acetic Acid → (2-{-4-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enylamino}-ethyl)-phosphonic acid diethyl ester

HRID 33640

反応式

HRID 33640 の反応式
[CH3:1][O:2][C:3]1[C:11]([CH3:12])=[C:10]2[C:6]([C:7](=[O:13])[O:8][CH2:9]2)=[C:5]([O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:4]=1[CH2:21][CH:22]=[C:23]([CH3:26])[CH:24]=O.C(O)(=O)C(O)=O.[CH2:33]([O:35][P:36]([CH2:41][CH2:42][NH2:43])(=[O:40])[O:37][CH2:38][CH3:39])[CH3:34].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>CN(C=O)C>[CH2:38]([O:37][P:36]([CH2:41][CH2:42][NH:43][CH2:24][C:23]([CH3:26])=[CH:22][CH2:21][C:4]1[C:5]([O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:18])[CH3:19])=[C:6]2[C:10](=[C:11]([CH3:12])[C:3]=1[O:2][CH3:1])[CH2:9][O:8][C:7]2=[O:13])(=[O:40])[O:35][CH2:33][CH3:34])[CH3:39]

参加物

6

反応物 4

HCID 176Acetic AcidHCID 2733595Diethyl (2-aminoethyl)phosphonate oxalateHCID 5049666Sodium triacetoxyborohydrideHCID 765461944-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enal

生成物 1

HCID 76541029(2-{-4-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enylamino}-ethyl)-phosphonic acid diethyl ester収率 96.5%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-2-methyl-but-2-enal (84 mg, 0.22 mmol), (2-amino-ethyl)-phosphonic acid diethyl ester oxalate (91 mg, 0.33 mmol), and sodium triacetoxyborohydride (93 mg, 0.44 mmol) in DMF (1.5 mL) was added acetic acid (60 μL, 1.0 mmol) at room temperature. The solution was stirred for 2 days when it was quenched by addition of saturated aqueous sodium bicarbonate solution and EtOAc. The organic layer was separated and concentrated under reduced pressure. The residue was purified by RP HPLC using a C18 column with a gradient of H2O, 0.1% TFA-acetonitrile, 0.1% TFA to provide 115 mg (96%) of the product as an oil. 1H NMR (300 MHz, CDCl3) δ 0.04 (s, 9H), 1.16-1.27 (m, 2H), 1.34 (t, 6H, J=7 Hz), 1.94 (s, 3H), 2.18 (s, 3H), 2.20-2.31 (m, 2H), 3.13-3.31 (m, 2H), 3.48 (d, 2H, J=7 Hz), 3.54 (s, 2H), 3.78 (s, 3H), 4.14 (pent, 4H, J=7 Hz), 4.30-4.37 (m, 2H), 5.13 (s, 2H), 5.65 (t, 1H, J=7 Hz), 6.23 (br s, 2H) ppm; 31P (121.4 MHz, CDCl3) δ 27.8 ppm; MS (m/z) 542.3 [M+H]+, 564.2 [M+Na]+.

後処理

  1. customwas quenched by addition of saturated aqueous sodium bicarbonate solution and EtOAc
  2. customThe organic layer was separated
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by RP HPLC

出典と根拠

ORDレコード
ord-1a760b141ac64817955670ae9d1787a1
出典データセット
uspto-grants-2008_09
特許番号
US07429565B2

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