(2,2-Dimethyl-1,3-dioxan-5-yl)methyl methanesulfonate → 4-{3-[4-(2,2-Dimethyl-[1,3]dioxan-5-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-2-isobutyl-6-methyl-pyridine

HRID 2040816ノート

反応式

HRID 2040816 の反応式
[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[N:17]=[C:16]([CH2:21][CH:22]([CH3:24])[CH3:23])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[OH:26])[CH3:2].[CH3:27][C:28]1([CH3:40])[O:33][CH2:32][CH:31]([CH2:34]OS(C)(=O)=O)[CH2:30][O:29]1>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[CH3:27][C:28]1([CH3:40])[O:33][CH2:32][CH:31]([CH2:34][O:26][C:4]2[C:5]([CH3:25])=[CH:6][C:7]([C:9]3[N:13]=[C:12]([C:14]4[CH:19]=[C:18]([CH3:20])[N:17]=[C:16]([CH2:21][CH:22]([CH3:23])[CH3:24])[CH:15]=4)[O:11][N:10]=3)=[CH:8][C:3]=2[CH2:1][CH3:2])[CH2:30][O:29]1

参加物

6

反応物 2

HCID 10998661(2,2-Dimethyl-1,3-dioxan-5-yl)methyl methanesulfonateHCID 1359239042-Ethyl-4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol

生成物 1

HCID 685526404-{3-[4-(2,2-Dimethyl-[1,3]dioxan-5-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-2-isobutyl-6-methyl-pyridine

試薬・触媒・溶媒 3

HCID 3776Isopropanol溶媒HCID 8857Ethyl Acetate溶媒HCID 14798Sodium Hydroxide溶媒

反応条件

温度
60 °C

実験手順

To a solution of 2-ethyl-4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol (200 mg, 0.569 mmol) in isopropanol (10 mL) and 3 N aq. NaOH (3 mL), methanesulfonic acid 2,2-dimethyl-[1,3]dioxan-5-ylmethyl ester (290 mg, 1.71 mmol) is added. The mixture is stirred at 60° C. for 24 h. The mixture is diluted with EA and washed with sat. aq. NaHCO3 solution. The org. extract is dried over MgSO4, filtered and evaporated. The crude product is purified by chromatography on prep. TLC plates with heptane:EA 3:1 to give 4-{3-[4-(2,2-dimethyl-[1,3]dioxan-5-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-2-isobutyl-6-methyl-pyridine which is dissolved in THF (5 mL), water (0.5 mL) and TFA (0.25 mL). The solution is stirred at rt for 1 h before the solvent is evaporated. The remaining residue is separated by chromatography on prep. TLC plates with DCM containing 10% of MeOH to give 2-{2-ethyl-4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxymethyl}-propane-1,3-diol (20 mg) as a colourless oil; LC-MS: tR=0.86 min, [M+1]+=440.12.

後処理

  1. washwashed with sat. aq. NaHCO3 solution
  2. extractionextract
  3. dry with materialis dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product is purified by chromatography on prep

出典と根拠

ORDレコード
ord-1d3e61f64b7d48d0831f6e32cc120965
出典データセット
uspto-grants-2013_11
特許番号
US08580824B2

反応ノート

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