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

HRID 2040815ノート

反応式

HRID 2040815 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].Cl[CH2:28][C@H:29]([OH:32])[CH2:30][OH:31]>C(O)(C)C.[OH-].[Na+].CC(=O)OCC>[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]([CH3:23])[CH3:24])[CH:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[O:26][CH2:28][C@H:29]([OH:32])[CH2:30][OH:31])[CH3:2]

参加物

6

反応物 2

HCID 148793(2R)-3-Chloro-1,2-propanediol2 回HCID 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 250314023-{2-ethyl-4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-(R)-propane-1,2-diol収率 16.5%

試薬・触媒・溶媒 3

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

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), (R)-3-chloro-1,2-propanediol (252 mg, 2.28 mmol) is added. The mixture is stirred at 60° C. for 24 h before another portion of (R)-3-chloro-1,2-propanediol (252 mg, 2.28 mmol) is added. Stirring is continued at 60° C. for 6 days. 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 EA to give 3-{2-ethyl-4-[5-(2-isobutyl-6-methyl-pyridin-4-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-(R)-propane-1,2-diol (40 mg) as a pale yellow oil; LC-MS: tR=0.84 min; [M+1]+=426.16; 1H NMR (CDCl3): δ 7.90 (s, 1H), 7.88 (s, 1H), 7.76 (s, 1H), 7.70 (s, 1H), 4.20-4.14 (m, 1H), 3.95-3.85 (m, 4H), 2.80-2.74 (m, 4H), 2.70 (s, 3H), 2.42 (s, 3H), 2.24-2.16 (m, 1H), 1.34 (t, J=7.5 Hz, 3H), 1.00 (d, J=6.5 Hz, 6 H).

後処理

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

出典と根拠

ORDレコード
ord-0b76f66aa8f3494bab6ac51f75b27ce3
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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