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

HRID 482987Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 482987
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]

Komponenten

5

Edukt 3

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

Produkt 1

HCID 132167461-{4-[(2,5-Difluorophenyl)methoxy]-4-ethynylpiperidin-1-yl}ethan-1-oneAusbeute 59,83 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
10 °C

Versuchsvorschrift

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),

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-9193aab6aa7e47229a30c16f4739d310
Quelldatensatz
uspto-grants-1986_03
Patentnummer
US04577026

Notizen zur Reaktion

Wird geladen…