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 32976

Reaktionsgleichung

Reaktionsgleichung von HRID 32976
[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]

Komponenten

6

Edukt 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

Produkt 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 esterAusbeute 96,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-22556513f4604147bbcc6339209508d4
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07427636B2

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