Water → 4-{[(3R)-1-Benzylpiperidin-3-yl]oxy}-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine

HRID 2189076ノート

反応式

HRID 2189076 の反応式
[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([OH:14])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].Cl[C:18]1[C:19]2[C:26]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)=[C:25]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[F:41])[O:24][C:20]=2[N:21]=[CH:22][N:23]=1.O>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14][C:18]2[C:19]3[C:26]([C:27]4[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[CH:31][CH:32]=4)=[C:25]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[F:41])[O:24][C:20]=3[N:21]=[CH:22][N:23]=2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

8

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 693761(R)-(-)-1-Benzyl-3-hydroxypiperidineHCID 580168704-Chloro-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine

生成物 1

HCID 671602904-{[(3R)-1-Benzylpiperidin-3-yl]oxy}-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine

試薬・触媒・溶媒 3

HCID 67553Tetrabutylammonium Iodide触媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

Dissolve 1037 mg (5.37 mmol) of (3R)-1-benzylpiperidin-3-ol [H. Tomori, Bull. Chem. Soc. Jpn. 69, 1, 207-216 (1996)] in 10 ml of THF and add 268 mg (6.71 mmol) of sodium hydride (60% in mineral oil). After 10 minutes, add a solution of 2000 mg (5.64 mmol) of 4-chloro-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine in 10 ml of THF and 99 mg (0.27 mmol) of tetra-n-butylammonium iodide. Heat the reaction mixture under reflux for 16 hours. Then add 100 ml of water and 100 ml of ethyl acetate. Remove the organic phase and wash with 50 ml of 1N hydrochloric acid and 100 ml of satd. sodium chloride solution. Re-extract the aqueous phase with 50 ml of ethyl acetate, dry the combined organic extracts over sodium sulphate, filter and concentrate under reduced pressure. 2645 mg (89% of theory, 92% purity) of the desired product are obtained.

後処理

  1. temperatureHeat the reaction mixture
  2. temperatureunder reflux for 16 hours
  3. customRemove the organic phase
  4. washwash with 50 ml of 1N hydrochloric acid and 100 ml of satd
  5. dry with materialRe-extract the aqueous phase with 50 ml of ethyl acetate, dry the combined organic extracts over sodium sulphate
  6. filtrationfilter
  7. concentrationconcentrate under reduced pressure

出典と根拠

ORDレコード
ord-19db67608c9c4062a6182399b5960012
出典データセット
uspto-grants-2012_12
特許番号
US08324222B2

反応ノート

読み込み中…