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

HRID 1278518노트

반응식

HRID 1278518 반응식
[H-].[H-].[H-].[H-].[Li+].[Al+3].C([O:9][C:10]([C@H:12]1[C@H:17]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[CH2:16][C:15](=O)[N:14]([CH3:26])[C:13]1=O)=O)C.C1(C)C=CC=CC=1.[OH-].[Na+]>C1(C)C=CC=CC=1.C1COCC1.C1COCC1.O>[F:24][C:21]1[CH:22]=[CH:23][C:18]([C@@H:17]2[CH2:16][CH2:15][N:14]([CH3:26])[CH2:13][C@H:12]2[CH2:10][OH:9])=[CH:19][CH:20]=1

참가 물질

8

반응물 4

HCID 1140TolueneHCID 14798Sodium HydroxideHCID 15405466trans-3-Ethoxycarbonyl-4-(4'-fluorophenyl)-1-methylpiperidine-2,6-dioneHCID 21226445Aluminium lithium hydride

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매2회HCID 8028Tetrahydrofuran용매HCID 22635083Tetrahydrofuran toluene용매

실험 절차

To a cooled solution of LiAlH4 (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, the reaction was allowed to warm to room temperature. After 30 minutes at room temperature reaction was heated to >40° C. for 2 hr. 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 was 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 higher yield (but similar impurity profile) as with NaAlH4 as shown by HPLC analysis. The product can be recovered by standard procedures such as trituration with a less polar solvent.

후처리

  1. additionAfter addition
  2. customAfter 30 minutes at room temperature reaction
  3. temperaturewas heated to >40° C. for 2 hr
  4. customReaction
  5. temperaturewas then cooled to <5° C.
  6. customthe temperature below 15° C
  7. customThe solid inorganic salts were removed by filtration
  8. washThese solids were washed with additional THF or toluene
  9. concentrationThe filtered solution was then concentrated

출처 및 근거

ORD 기록
ord-2aa132d7e98c4a0ea35b10fc28db711d
출처 데이터셋
uspto-grants-2002_09
특허 번호
US06444190B2

반응 노트

불러오는 중…