HCID 86684774、化合物 → HCID 66685241、化合物

HRID 579208ノート

反応式

HRID 579208 の反応式
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][CH:23]=[O:24])[C:11]1=[O:25])=[O:4].[CH3:32][Mg+].[Br-]>C1COCC1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][C@H:23]([OH:24])[CH3:32])[C:11]1=[O:25])=[O:4].[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:26]#[C:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:8][C:9]=1[N:10]1[C@H:15]([CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)[CH2:14][O:13][C@H:12]([CH2:22][C@@H:23]([OH:24])[CH3:32])[C:11]1=[O:25])=[O:4]

参加物

5

反応物 2

HCID 86684774HCID 86684774、化合物HCID 178418689HCID 178418689、化合物

生成物 2

HCID 66683972HCID 66683972、化合物収率 29%HCID 66685241HCID 66685241、化合物収率 40.7%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-10 °C

実験手順

To a solution of 3-[(2R,5R)-5-cyclohexyl-3-oxo-2-(2-oxo-ethyl)-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (1.9 g, 4.26 mmol, 1.0 equiv) in THF (200 mL) at −10° C., was added MeMgBr (1.85 mL, 3.0 M solution in THF, 5.54 mmol, 1.3 equiv). The resulting solution was stirred at −10° C. for 20 minutes. The reaction was quenched by addition of 3.0 N HCl aqueous solution until pH=1. The volatile solvent was removed under vacuum and the residue was partitioned between EtOAc (100 mL) and brine (5 mL). The separated organic layer was dried over Na2SO4 and concentrated. The residue was purified by silica gel column chromatography [Et2O (2% EtOAc)/Heptane, 25% to 50%] to give 3-[(2R,5R)-5-Cyclohexyl-2-((R)-2-hydroxy-propyl)-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (0.57 g, 29.0%) and 3-[(2R,5R)-5-Cyclohexyl-2-((S)-2-hydroxy-propyl)-3-oxo-morpholin-4-yl]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (0.80 g, 40.7%). MS: 462.4 [M−H+].

後処理

  1. customThe reaction was quenched by addition of 3.0 N HCl aqueous solution until pH=1
  2. customThe volatile solvent was removed under vacuum
  3. customthe residue was partitioned between EtOAc (100 mL) and brine (5 mL)
  4. dry with materialThe separated organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography [Et2O (2% EtOAc)/Heptane, 25% to 50%]

出典と根拠

ORDレコード
ord-ecd8a7672bf740e69cb85edc9e9206a5
出典データセット
uspto-grants-2015_05
特許番号
US09040690B2

反応ノート

読み込み中…