Carbonocyanidic acid, methyl ester → (4-(1-(cyclopropylmethyl)-2-neopentyl-1H-benzo[d]imidazol-5-ylsulfonyl)-1-tritylpiperidin-4-yl)methanol

HRID 241648ノート

反応式

HRID 241648 の反応式
[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([S:14]([CH:17]4[CH2:22][CH2:21][N:20]([C:23]([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)([C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)[C:24]5[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=5)[CH2:19][CH2:18]4)(=[O:16])=[O:15])=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:3][CH2:2]1.C([N-]C(C)C)(C)C.[Li+].C([C:57](OC)=[O:58])#N>O1CCCC1>[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([S:14]([C:17]4([CH2:57][OH:58])[CH2:18][CH2:19][N:20]([C:23]([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)([C:24]5[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=5)[C:30]5[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=5)[CH2:21][CH2:22]4)(=[O:15])=[O:16])=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:42][C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:3][CH2:2]1

参加物

5

反応物 3

HCID 28660Carbonocyanidic acid, methyl esterHCID 2724682Lithium diisopropylamideHCID 585135841-(cyclopropylmethyl)-2-neopentyl-5-(1-tritylpiperidin-4-ylsulfonyl)-1H-benzo[d]imidazole

生成物 1

HCID 58513617(4-(1-(cyclopropylmethyl)-2-neopentyl-1H-benzo[d]imidazol-5-ylsulfonyl)-1-tritylpiperidin-4-yl)methanol

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-40 °C

実験手順

To a solution of 1-(cyclopropylmethyl)-2-neopentyl-5-(1-tritylpiperidin-4-ylsulfonyl)-1H-benzo[d]imidazole (STEP E, 2.05 g, 3.24 mmol) in tetrahydrofuran (60 mL) at −60° C. was added lithium diisopropylamide (1.8 mol/L heptane/tetrahydrofuran/ethylbenzene solution, 2.34 mL, 4.22 mmol). After the mixture was warmed up to −40° C. over a period of 20 min and then stirred for 40 min at the same temperature, methyl cyanoformate (828 mg, 9.73 mmol) in tetrahydrofuran (3 mL) was added to the mixture. The mixture was stirred at 0° C. for 1.5 h. The reaction was quenched with water and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (dichloromethane-ethyl acetate, gradient) to give 4:1 mixture of the title compound and the starting material (2.15 g).

後処理

  1. additionwas added to the mixture
  2. customThe reaction was quenched with water
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography (dichloromethane-ethyl acetate, gradient)
  8. customto give

出典と根拠

ORDレコード
ord-c6072575b2094ada9fec4dd23fae7ec2
出典データセット
uspto-grants-2014_02
特許番号
US08653063B2

反応ノート

読み込み中…