Citric Acid → 5(S)-[1(S)-(Boc-Amino)-2-phenylethyl]-3(R)-[(2,4-dimethoxyphenyl)methyl]-dihydrofuran-2-(3H)-one

HRID 2394142ノート

反応式

HRID 2394142 の反応式
[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[CH2:19][CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1C(=O)N(C)CCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:42][O:43][C:44]1[CH:51]=[C:50]([O:52][CH3:53])[CH:49]=[CH:48][C:45]=1[CH2:46]Br.C(O)(=O)CC.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C(OCC)(=O)C.O.C1(C)C=CC=CC=1>[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:46][C:45]2[CH:48]=[CH:49][C:50]([O:52][CH3:53])=[CH:51][C:44]=2[O:43][CH3:42])[CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]

参加物

11

反応物 6

HCID 311Citric AcidHCID 1032Propionic AcidHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-HCID 2733832Lithium HexamethyldisilazideHCID 10870461tert-butyl(1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamateHCID 151519071-(Bromomethyl)-2,4-dimethoxybenzene

生成物 1

HCID 701496735(S)-[1(S)-(Boc-Amino)-2-phenylethyl]-3(R)-[(2,4-dimethoxyphenyl)methyl]-dihydrofuran-2-(3H)-one

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

A solution of 3.57 g (11.7 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]dihydrofuran-2-(3H)-one [Example 2b)] in 12 ml of abs. THF and 2.35 ml of DMPU (1.65 equivalents) is cooled down to -75° C., under argon, and is treated dropwise, at an internal temperature of less than -70° C. and over a period of 30 min, with 22.9 ml (1.96 equivalents) of a 1M solution of lithium bis(trimethylsilyl)amide in THF (Aldrich, Steinheim, FRG). After a further 15 min, 25 ml of a toluene solution containing approximately 1 equivalent of 2,4-dimethoxybenzyl bromide is added dropwise to this mixture, over the space of 20 min, and this mixture is allowed to react at -70° C. for 2 h. 4.36 ml of propionic acid and 4.36 ml of water are then added to this solution and the temperature is allowed to rise to 0° C. The reaction mixture is diluted with 200 ml of (cold) ethyl acetate and stirred up for 5 min with 60 ml of (cold) 10% citric acid. After that, the phases are separated. The organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution and with saline once again, dried over Na2SO4 and concentrated. The title compound is isolated by flash chromatography on silica gel (E). TLC Rf (E)=0.24.-FAB-MS (M+H)+ =455.-HPLC tRet =16.85 min (gradient II). IR(CH2 Cl2)=inter alia 3429, 1769, 1712, 1613 and 1506 cm-1.-1 H-NMR(CDCl3)=inter alia 7.34-7.10/m (5H); 6.98/d (1H); 6.45-6.291m (2H); 4.31/txd (1H); 3.78 and 3.71/each s (each 3H); 3.08 and 2.66/each d×d (each 1H); 1.35/s (9H).

後処理

  1. additionis added dropwise to this mixture, over the space of 20 min
  2. customto react at -70° C. for 2 h
  3. customto rise to 0° C
  4. customAfter that, the phases are separated
  5. washThe organic phase is washed, in succession, with saline, sat. sodium bicarbonate solution and with saline once again
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-adb9bf21976245cbbe9e791bef2d27a0
出典データセット
uspto-grants-1998_09
特許番号
US05807891

反応ノート

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