Cesium carbonate → (R)-2-[4-(4-Pyridin-3-yl-phenoxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1909713ノート

反応式

HRID 1909713 の反応式
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[CH:2]=1.[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@@H:22]1[CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31](I)=[CH:30][CH:29]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.CN(C)CC(O)=O>O1CCOCC1.CCOC(C)=O.O>[C:14]([O:18][C:19]([N:21]1[CH2:25][CH2:24][CH2:23][C@@H:22]1[CH2:26][O:27][C:28]1[CH:29]=[CH:30][C:31]([O:13][C:10]2[CH:11]=[CH:12][C:7]([C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)=[CH:8][CH:9]=2)=[CH:32][CH:33]=1)=[O:20])([CH3:17])([CH3:15])[CH3:16]

参加物

8

反応物 4

HCID 10796Cesium carbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 153040Phenol, 4-(3-pyridinyl)-HCID 44819166(R)-2-(4-Iodo-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 69003810(R)-2-[4-(4-Pyridin-3-yl-phenoxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester収率 48.2%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒3 回

反応条件

温度
90 °C

実験手順

To a solution of product from step 2 (114 mg, 0.66 mmol) in dioxane (2 mL) was added (R)-2-(4-iodo-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (403 mg, 1.0 mmol) in dioxane (1.5 mL) and cesium carbonate (432 mg, 1.33 mmol). The vessel was purged with nitrogen for 15 min before N,N-dimethylglycine hydrochloride (9 mg, 0.06 mmol) in dioxane (0.5 mL) and Cu(I) iodide (4 mg, 0.02 mmol) were added. The resulted mixture was stirred at 90° C. for 48 h. It was then diluted with EtOAc and water, organic layer was separated, washed with water, brine, dried over anhydrous MgSO4 and concentrated in vacuo to yellow oil. The crude mixture was purified by silica gel flash chromatography (15% EtOAc/Hexane) to obtain the title product as yellow oil (142 mg, 48%).

後処理

  1. additionwere added
  2. customwas separated
  3. washwashed with water, brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo to yellow oil
  6. customThe crude mixture was purified by silica gel flash chromatography (15% EtOAc/Hexane)

出典と根拠

ORDレコード
ord-fe708bb1ddaa4fdfaf90ef48192f7856
出典データセット
uspto-grants-2013_12
特許番号
US08598359B2

反応ノート

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