Diisopropylethylamine → (2S,5R)-6-(benzyloxy)-3-(((tert-butyldimethylsilyl)oxy)methyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-ene-2-carboxamide

HRID 627187ノート

反応式

HRID 627187 の反応式
[CH2:1]([O:8][NH:9][C@H:10]1[CH2:15][NH:14][CH:13]([C:16]([NH2:18])=[O:17])[C:12]([CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])=[CH:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(C(C)C)CC)(C)C.Cl[C:38](Cl)([O:40]C(=O)OC(Cl)(Cl)Cl)Cl>C(#N)C.C(OCC)(=O)C>[CH2:1]([O:8][N:9]1[C:38](=[O:40])[N:14]2[CH2:15][C@H:10]1[CH:11]=[C:12]([CH2:19][O:20][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:22])[CH3:23])[C@H:13]2[C:16]([NH2:18])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 94429Triphosgene2 回HCID 123580399(5R)-5-((benzyloxy)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1,2,5,6-tetrahydropyridine-2-carboxamide2 回

生成物 1

HCID 89852172(2S,5R)-6-(benzyloxy)-3-(((tert-butyldimethylsilyl)oxy)methyl)-7-oxo-1,6-diazabicyclo[3.2.1]oct-3-ene-2-carboxamide収率 110%

試薬・触媒・溶媒 2

HCID 6342Acetonitrile溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To a solution of (5R)-5-((benzyloxy)amino)-3-(((tert-butyldimethylsilyl)oxy)methyl)-1,2,5,6-tetrahydropyridine-2-carboxamide (Intermediate 163, 0.562 g, 1.44 mmol) and diisopropylethyl amine (1.000 mL, 5.74 mmol) in acetonitrile (200 mL) at 0° C. was added triphosgene (0.145 g, 0.49 mmol) as a solution in acetonitrile (6 mL). The triphosgene solution was added at a rate of 4 mL/hour. Once addition was complete the reaction was stirred at 0° C. overnight. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate. The aqueous layer was extracted again with EtOAc and then DCM. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (0%-100, ethyl acetate/hexanes) afforded the title compound (0.225 g, 37.5%) as a colorless film.

後処理

  1. additionOnce addition
  2. washwashed with saturated sodium bicarbonate
  3. extractionThe aqueous layer was extracted again with EtOAc
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

出典と根拠

ORDレコード
ord-b0436d15329e42ec9a3e81fcc3d29bca
出典データセット
uspto-grants-2016_04
特許番号
US09309245B2

反応ノート

読み込み中…