(2R)-3-Chloro-1,2-propanediol → (2R)-3-{4-[5-(5-ethyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propane-1,2-diol

HRID 1094300ノート

反応式

HRID 1094300 の反応式
[CH2:1]([C:3]1[S:7][C:6]([C:8]2[O:12][N:11]=[C:10]([C:13]3[CH:18]=[C:17]([CH3:19])[C:16]([OH:20])=[C:15]([CH3:21])[CH:14]=3)[N:9]=2)=[CH:5][CH:4]=1)[CH3:2].Cl[CH2:23][C@H:24]([OH:27])[CH2:25][OH:26]>C(O)(C)C.[OH-].[Na+].O>[CH2:1]([C:3]1[S:7][C:6]([C:8]2[O:12][N:11]=[C:10]([C:13]3[CH:18]=[C:17]([CH3:19])[C:16]([O:20][CH2:23][C@H:24]([OH:27])[CH2:25][OH:26])=[C:15]([CH3:21])[CH:14]=3)[N:9]=2)=[CH:5][CH:4]=1)[CH3:2]

参加物

6

反応物 2

HCID 148793(2R)-3-Chloro-1,2-propanediol2 回HCID 1360299474-[5-(5-Ethyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenol

生成物 1

HCID 59202034(2R)-3-{4-[5-(5-ethyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propane-1,2-diol

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 3776Isopropanol溶媒HCID 14798Sodium Hydroxide溶媒

実験手順

To a solution of 4-[5-(5-ethyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenol (79 mg, 0.263 mmol) in isopropanol (3 mL) and 3 N aq. NaOH (0.6 mL), (R)-3-chloro-propane-1,2-diol (148 mg, 1.31 mmol) is added. The mixture is stirred at rt for 2 h, then at 65° C. for 16 h before another portion of (R)-3-chloro-propane-1,2-diol (119 mg, 1.05 mmol) is added. Stirring is continued at 65° C. for 24 h. The reaction mixture is diluted with water and extracted with diethyl ether. The org. extract is dried over MgSO4, filtered and evaporated. The crude product is purified by chromatography on prep. TLC plates with DCM containing 4% of 7 N NH3 in methanol to give (2R)-3-{4-[5-(5-ethyl-thiophen-2-yl)-[1,2,4]oxadiazol-3-yl]-2,6-dimethyl-phenoxy}-propane-1,2-diol as an off-white solid; LC-MS: tR=0.99 min; [M+1]+=375.13; 1H NMR (CDCl3): δ 7.83 (s, 2H), 7.80 (d, J=3.8 Hz, 1H), 6.93 (d, J=3.8 Hz, 1H), 4.20-4.11 (m, 1H), 3.97-3.93 (m, 1H), 3.91 (dd, J=11.5, 4.3 Hz, 1H), 3.85 (dd, J=11.5, 5.5 Hz, 1H), 2.97 (q, J=7.5 Hz, 2H), 2.39 (s, 6H), 1.41 (t, J=7.5 Hz, 3H).

後処理

  1. stirringStirring
  2. waitis continued at 65° C. for 24 h
  3. extractionextracted with diethyl ether
  4. extractionextract
  5. dry with materialis dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product is purified by chromatography on prep

出典と根拠

ORDレコード
ord-a36e7f62ef1a418293328db8f272ec7a
出典データセット
uspto-grants-2012_03
特許番号
US08133910B2

反応ノート

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