Triethylamine → ({-6-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoylamino}-methyl)-phosphonic acid diethyl ester

HRID 910556Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 910556
[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]([CH3:29])[CH2:24][CH2:25][C:26](O)=[O:27].ClC(OCC(C)C)=O.C(N(CC)CC)C.C(O)(=O)C(O)=O.[CH2:51]([O:53][P:54]([CH2:59][NH2:60])(=[O:58])[O:55][CH2:56][CH3:57])[CH3:52]>C1COCC1>[CH2:51]([O:53][P:54]([CH2:59][NH:60][C:26](=[O:27])[CH2:25][CH2:24][C:23]([CH3:29])=[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:58])[O:55][CH2:56][CH3:57])[CH3:52]

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 2733594diethyl (aminomethyl)phosphonate oxalate saltHCID 670102826-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic Acid

Produkt 1

HCID 76541034({-6-[6-Methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoylamino}-methyl)-phosphonic acid diethyl esterAusbeute 81 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 6-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-4-methyl-hex-4-enoic acid (50 mg, 0.12 mmol) in THF (1 mL) was added isobutyl chloroformate (17 μL, 0.13 mmol) and triethylamine (50 μL, 0.36 mmol) at 0° C. After stirring at 0° C. for 2 hours, diethyl(aminomethyl)phosphonate oxalate (62 mg, 0.26 mmol) was added and stirring was continued at room temperature for 20 minutes. After removal of solvent, the residue was purified by preparative reverse-phase HPLC to afford 54.8 mg (81%) of the desired product. 1H NMR (300 MHz, CDCl3) δ 0.03 (s, 9H), 1.15-1.22 (m, 2H), 1.31 (t, 6H), 1.81 (s, 3H), 2.18 (s, 3H), 2.30 (m, 4H), 3.41 (d, 2H, J=7 Hz), 3.65 (dd, 2H, J=6, 12 Hz), 3.77 (s, 3H), 3.77-4.16 (m, 4H), 4.26-4.32 (m, 2H), 5.12 (s, 2H), 5.17-5.19 (m, 1H), 5.86 (bs, 1H) ppm; 31P (121.4 MHz, CDCl3) δ 23.01 ppm; MS (m/z) 568 [M−H]−, 592 [M+Na]+.

Aufarbeitung

  1. stirringstirring
  2. waitwas continued at room temperature for 20 minutes
  3. customAfter removal of solvent
  4. customthe residue was purified by preparative reverse-phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-d28b4d950fef433fa5134bd943140dd9
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08022083B2

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