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

HRID 750087ノート

反応式

HRID 750087 の反応式
[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1.[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@@H:21]1[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30](I)=[CH:29][CH:28]=1)=[O:19])([CH3:16])([CH3:15])[CH3:14].Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.[Cu]I>[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@@H:21]1[CH2:25][O:26][C:27]1[CH:28]=[CH:29][C:30]([O:12][C:9]2[CH:10]=[CH:11][C:6]([C:2]3[S:1][CH:5]=[CH:4][N:3]=3)=[CH:7][CH:8]=2)=[CH:31][CH:32]=1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

参加物

7

反応物 4

HCID 10796Cesium carbonateHCID 75605N,N-Dimethylglycine hydrochlorideHCID 2238404-(1,3-Thiazol-2-yl)phenolHCID 44819166(R)-2-(4-Iodo-phenoxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 68996854(R)-2-[4-(4-Thiazol-2-yl-phenoxy)-phenoxymethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester収率 69%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 312751,4-Dioxane溶媒

実験手順

A mixture of the product of step 2 (0.1 g, 0.56 mmol), the product of Example 130, step 2 (0.30 g, 0.73 mmol), N,N-dimethylglycine HCl salt (0.20 g, 1.46 mmol), copper(I) iodide (0.19 g, 1.01 mmol) and cesium carbonate (0.28 g, 0.85 mmol) in dioxane (2 ml) was heated 100° C. for 60 h under nitrogen. The solids were filtered off, and the filtrate was concentrated in vacuo. The residue was purified by a column chromatography on silica gel eluting with 25% EtOAc/hexanes to yield the title product (130 mg, 69%); 1HNMR (400 MHz, CDCl3) δ 7.88 (d, J=8.4 Hz, 2H), 7.84 (d, J=3.2 Hz, 1H), 7.30 (d, J=3.2 Hz, 1H), 7.24 (d, J=8.4 Hz, 2H), 7.10 (d, J=8 Hz, 2H), 6.86 (br d, J=8 Hz, 2H), 4.10 (br, 2H), 3.96 (s, 2H), 3.40 (br, 2H), 2.03-1.80 (m, 4H), 1.46 (s, 9H).

後処理

  1. filtrationThe solids were filtered off
  2. concentrationthe filtrate was concentrated in vacuo
  3. customThe residue was purified by a column chromatography on silica gel eluting with 25% EtOAc/hexanes

出典と根拠

ORDレコード
ord-1632ea7f619540a1b166476bf06808ce
出典データセット
uspto-grants-2008_07
特許番号
US07402684B2

反応ノート

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