1,2-Dimethoxyethane → 4-{2-(2-Ethoxycarbonyl-ethyl)-3-[6-(5-hydroxymethyl-4'-methanesulfonyl-biphenyl-3-yloxy)-hexyl]-phenoxy}-butyric acid ethyl ester

HRID 416967ノート

反応式

HRID 416967 の反応式
[CH2:1]([O:3][C:4](=[O:38])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[C:26]([CH2:28][OH:29])[CH:25]=[C:24](Br)[CH:23]=2)[C:10]=1[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH3:2].[CH3:39][S:40]([C:43]1[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=1)(=[O:42])=[O:41].C(=O)([O-])[O-].[Cs+].[Cs+].C(COC)OC>O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:1]([O:3][C:4](=[O:38])[CH2:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:23]=[C:24]([C:46]3[CH:47]=[CH:48][C:43]([S:40]([CH3:39])(=[O:42])=[O:41])=[CH:44][CH:45]=3)[CH:25]=[C:26]([CH2:28][OH:29])[CH:27]=2)[C:10]=1[CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])[CH3:2]

参加物

8

反応物 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 594968024-[3-[6-(3-Bromo-5-hydroxymethyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester

生成物 1

HCID 594968084-{2-(2-Ethoxycarbonyl-ethyl)-3-[6-(5-hydroxymethyl-4'-methanesulfonyl-biphenyl-3-yloxy)-hexyl]-phenoxy}-butyric acid ethyl ester収率 55.1%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
96 °C

実験手順

To a mixture of 4-[3-[6-(3-bromo-5-hydroxymethyl-phenoxy)-hexyl]-2-(2-ethyoxycarbonyl-ethyl)-phenoxy]-butyric acid ethyl ester (2.0 g, 3.34 mmol), 4-methanesulfonylphenylboronic acid (1.35 g, 6.74 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (369.8 mg, 0.51 mmol), and cesium carbonate (2.22 g, 6.74 mmol) was added dimethoxyethane (100 mL) at room temperature under nitrogen atmosphere. The resulting brown reaction mixture was heated to 96° C. and stirred for 15 h at which time the TLC analysis of the reaction mixture indicated the absence of starting material. Then, the reaction mixture was cooled to room temperature and diluted with water and ethyl acetate. The two layers were separated and the aqueous layer was extracted with ethyl acetate and the combined organic extracts were washed with water and brine solution. The organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent under vacuum gave the colored residue which was purified by using an ISCO 120 g column to obtain 4-{2-(2-ethoxycarbonyl-ethyl)-3-[6-(5-hydroxymethyl-4′-methanesulfonyl-biphenyl-3-yloxy)-hexyl]-phenoxy}-butyric acid ethyl ester (1.23 g, 55%) as a light brown oil: ES(+)-HRMS m/e calcd for C37H48O9S (M+Na)+ 691.2911. found 691.2913.

後処理

  1. temperatureThen, the reaction mixture was cooled to room temperature
  2. customThe two layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate
  4. washthe combined organic extracts were washed with water and brine solution
  5. dry with materialThe organic layer was dried over anhydrous magnesium sulfate and filtration of the drying agent and removal of the solvent under vacuum
  6. customgave the colored residue which
  7. customwas purified

出典と根拠

ORDレコード
ord-d5907cb048c84e6b971be5ffc4e454a2
出典データセット
uspto-grants-2012_01
特許番号
US08088936B2

反応ノート

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