2,6-Lutidine → [2-Ethyl-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-but-2-enyloxymethyl]-phosphonic acid

HRID 32999

反応式

HRID 32999 の反応式
C([O:4][P:5]([CH2:11][O:12][CH2:13][C:14]([CH2:37][CH3:38])=[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:10])[O:6]C(C)C)(C)C.N1C(C)=CC=CC=1C.Br[Si](C)(C)C>C(#N)C>[CH2:37]([C:14](=[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])[CH2:13][O:12][CH2:11][P:5](=[O:4])([OH:6])[OH:10])[CH3:38]

参加物

5

反応物 3

HCID 79372,6-LutidineHCID 76113BromotrimethylsilaneHCID 76542764{2-Ethyl-4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-but-2-enyloxymethyl}-phosphonic Acid Diisopropyl Ester

生成物 1

HCID 67011098[2-Ethyl-4-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydro-isobenzofuran-5-yl)-but-2-enyloxymethyl]-phosphonic acid収率 87%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of {2-ethyl-4-[6-methoxy-7-methyl-3-oxo-4-(2-trimethylsilanyl-ethoxy)-1,3-dihydro-isobenzofuran-5-yl]-but-2-enyloxymethyl}-phosphonic acid diisopropyl ester (347 mg, 0.61 mmol) in acetonitrile (5 mL) was added 2,6-lutidine (0.71 mL, 6.1 mmol) and bromotrimethylsilane (0.786 mL, 6.1 mmol). The mixture was stirred at room temperature for 3 hours, quenched with methanol (5 mL), concentrated, and partitioned between ethyl acetate and 1N HCl (aqueous). The organic layer was concentrated to give the free phosphonic acid as a colorless oil (205 mg, 70%). This material (20 mg) was dissolved in a solution of trifluoroacetic acid (0.3 mL) and dichloromethane (2.7 mL) and stirred for 30 minutes at ambient temperature. After concentration, 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 the product, after lyophilization, as a white solid (10 mg). 1H NMR (300 MHz, CDCl3) δ 1.007 (t, 3H, J=7.5 Hz), 2.13 (s, 3H), 2.32 (q, 2H, J=7.5 Hz), 3.41 (d, 2H, J=6.3 Hz), 3.56 (d, 2H, J=9 Hz), 3.75 (s, 3H), 3.95 (s, 2H), 5.16 (s, 2H), 5.43 (t, 1H, J=6.3 Hz) ppm; 31P (121.4 MHz, CDCl3) δ 22.8 ppm; MS (m/z) 385.2 [M−H]+, 387.1 [M+H]+.

後処理

  1. customquenched with methanol (5 mL)
  2. concentrationconcentrated
  3. custompartitioned between ethyl acetate and 1N HCl (aqueous)
  4. concentrationThe organic layer was concentrated

出典と根拠

ORDレコード
ord-10464711ef81430a9bc0769e5ce85d9a
出典データセット
uspto-grants-2008_09
特許番号
US07427636B2

関連ノート

読み込み中…