2,5-Difluorobenzyl Chloride → 1-{4-[(2,5-Difluorophenyl)methoxy]-4-ethynylpiperidin-1-yl}ethan-1-one

HRID 1248025ノート

反応式

HRID 1248025 の反応式
CC(C)([O-])C.[K+].[C:7]([N:10]1[CH2:15][CH2:14][C:13]([C:17]#[CH:18])([OH:16])[CH2:12][CH2:11]1)(=[O:9])[CH3:8].[F:19][C:20]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:21]=1[CH2:22]Cl>CN(C=O)C>[C:7]([N:10]1[CH2:15][CH2:14][C:13]([C:17]#[CH:18])([O:16][CH2:22][C:21]2[CH:24]=[C:25]([F:28])[CH:26]=[CH:27][C:20]=2[F:19])[CH2:12][CH2:11]1)(=[O:9])[CH3:8]

参加物

5

反応物 3

HCID 27369502,5-Difluorobenzyl ChlorideHCID 132167351-(4-Ethynyl-4-hydroxypiperidin-1-yl)ethan-1-oneHCID 23665647Potassium tert-butoxide

生成物 1

HCID 132167461-{4-[(2,5-Difluorophenyl)methoxy]-4-ethynylpiperidin-1-yl}ethan-1-one収率 59.83%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
10 °C

実験手順

A solution of 7.04 g of potassium t-butoxide (62.9 mmole) in 20 ml of dry DMF was added dropwise to a chilled solution of 10 g of 1-acetyl-4-ethynyl-4-hydroxypiperidine (59.9 mmole) in 75 ml of dry DMF, at such a rate as to maintain the temperature at 10° C. The mixture was allowed to equilibrate at 10° C. for 15 min. after which time it was cooled to -20° C. To this solution was added 9.73 g of 2,5-difluorobenzylchloride (59.9 mmole) at such a rate as to maintain the temperature around -20° C. After complete addition, the reaction mixture was warmed to 0° C. and allowed to react for 1 hr. The reaction appeared to be complete by GLC and was quenched with ice and water. The products were extracted into ether and dried over K2CO3. After filtration, the solvent was removed under vacuum. The crystalline product was recrystallized from cyclohexane and dried, affording 10.5 g of 1-acetyl-4-ethynyl-4-(2,5-difluorophenylmethoxy)piperidine (35.8 mmole, 59.83%). This material appeared pure by GLC (99% on OV225, temperature program: 200° C. (2 min), rate=25° C./min, 250° C. (15 min), flow=30 ml/min tR =4.00 min) and ty TLC on silica gel in hexane:ethylacetate (1:1), Rf =0.2. MS (ci MH+ =294). NMR-CDCl3 and IR-CHCl3 were consistent with the structure; m.p.=90°-93° C.

後処理

  1. temperatureafter which time it was cooled to -20° C
  2. temperatureto maintain the temperature around -20° C
  3. additionAfter complete addition
  4. temperaturethe reaction mixture was warmed to 0° C.
  5. customto react for 1 hr
  6. customwas quenched with ice and water
  7. extractionThe products were extracted into ether
  8. dry with materialdried over K2CO3
  9. filtrationAfter filtration
  10. customthe solvent was removed under vacuum
  11. customThe crystalline product was recrystallized from cyclohexane
  12. customdried

出典と根拠

ORDレコード
ord-e7631ac1e114438ba656c78335856354
出典データセット
uspto-grants-1985_06
特許番号
US04521537

反応ノート

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