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

HRID 1278517ノート

反応式

HRID 1278517 の反応式
C([O:3][C:4]([C@H:6]1[C@H:11]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:10][C:9](=O)[N:8]([CH3:20])[C:7]1=O)=O)C.C1(C)C=CC=CC=1.O.[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.C1COCC1>[F:18][C:15]1[CH:16]=[CH:17][C:12]([C@@H:11]2[CH2:10][CH2:9][N:8]([CH3:20])[CH2:7][C@H:6]2[CH2:4][OH:3])=[CH:13][CH:14]=1

参加物

7

反応物 4

HCID 962Water2 回HCID 1140TolueneHCID 14798Sodium HydroxideHCID 15405466trans-3-Ethoxycarbonyl-4-(4'-fluorophenyl)-1-methylpiperidine-2,6-dione

生成物 1

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

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 22635083Tetrahydrofuran toluene溶媒

実験手順

To a cooled solution of NaAlH4 (0.22 mol) in toluene/THF under argon was added (+/−) trans-3-ethoxycarbonyl-4-(4′-fluorophenyl)-N-methyl-piperidine-2,6-dione (0.083 mol) in THF holding the temperature below 15° C. After addition was complete, reaction was allowed to warm to room temperature. After 30 minutes at room temperature, the reaction was heated to >40° C. for 2 hr. The reaction was then cooled to <5° C. and toluene (50 ml) was added. Water (9 ml) was then added slowly holding the temperature below 15° C. Additional H2O or aqueous NaOH were used as necessary. The solid inorganic salts were removed by filtration. These solids were washed with additional THF or toluene. The filtered solution was then concentrated to give (+/−) trans-4-(4′-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine in lower yield (but 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. additionAfter addition
  2. customreaction
  3. temperaturethe reaction was heated to >40° C. for 2 hr
  4. temperatureThe reaction was then cooled to <5° C.
  5. customthe temperature below 15° C
  6. customThe solid inorganic salts were removed by filtration
  7. washThese solids were washed with additional THF or toluene
  8. concentrationThe filtered solution was then concentrated

出典と根拠

ORDレコード
ord-575733b9661e402ab01bcd528da08b40
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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