Water → (-)-trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

HRID 1278520ノート

反応式

HRID 1278520 の反応式
[Li+].[Cl-].C([O:5][C:6]([C@H:8]1[C@H:13]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[CH2:12][C:11](=O)[N:10]([CH3:22])[C:9]1=O)=O)C.O.[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1>[F:20][C:17]1[CH:18]=[CH:19][C:14]([C@@H:13]2[CH2:12][CH2:11][N:10]([CH3:22])[CH2:9][C@H:8]2[CH2:6][OH:5])=[CH:15][CH:16]=1

参加物

7

反応物 4

HCID 962Water2 回HCID 14798Sodium HydroxideHCID 433294Lithium Chloride2 回HCID 15405466trans-3-Ethoxycarbonyl-4-(4'-fluorophenyl)-1-methylpiperidine-2,6-dione2 回

生成物 1

HCID 2734218(-)-trans-4-(4'-Fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒2 回HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a cooled mixture of NaAlH4 (0.22 mol) in toluene is added LiCl (0.11 mol) in THF. Note: LiCl can be added to the reactor prior to the addition of NaAlH4 or after the addition of the substrate, (+/−)trans 3-ethoxycarbonyl-4-(4′-fluorophenyl)-N-methyl-piperidine-2,6-dione. Next, (+/−)trans 3-ethoxycarbonyl-4-(4′-fluorophenyl)-N-methyl-piperidine-2,6-dione (0.083 mol) is added in THF (65 ml) holding the temperature below 15° C. After addition is completed, reaction is allowed to warm to room temperature. After 30 minutes at room temperature, the reaction is heated to >40° C. for 2 hr. The reaction is then cooled to <5° C. and toluene (50 ml) is added. Water (9 ml) is then added slowly holding the temperature below 15° C. Additional H2O or aqueous NaOH is used as necessary. The solid inorganic salts are removed by filtration. These solids are washed with additional THF or toluene. The filtered solution is then concentrated to give (+/−) trans-4-(4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine in essentially the same yield and similar impurity profile as with LiAlH4 as shown by HPLC analysis. The product can be recovered by standard procedures such as trituration with a less polar solvents.

後処理

  1. customthe temperature below 15° C
  2. additionAfter addition
  3. customreaction
  4. temperaturethe reaction is heated to >40° C. for 2 hr
  5. temperatureThe reaction is then cooled to <5° C.
  6. customthe temperature below 15° C
  7. customThe solid inorganic salts are removed by filtration
  8. washThese solids are washed with additional THF or toluene
  9. concentrationThe filtered solution is then concentrated

出典と根拠

ORDレコード
ord-10b6824bcbc0490f9bb5c5e5887e5132
出典データセット
uspto-grants-2002_09
特許番号
US06444190B2

反応ノート

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