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

HRID 1589437노트

반응식

HRID 1589437 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
10 °C

실험 절차

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 by 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.

후처리

  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

출처 및 근거

ORD 기록
ord-38c3e359c52c4dda9a71a1e3837de717
출처 데이터셋
uspto-grants-1986_02
특허 번호
US04569998

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