3,3-Dimethyl-1-butyne → methyl {(2S,3R)-1-[(1S)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pent-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-3-yl}acetate

HRID 1942312Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1942312
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:8]=[CH:7][C:6]([C@@H:9]2[C@@H:14]([CH2:15][C:16]([O:18][CH3:19])=[O:17])[CH2:13][CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.[F:22][C:23]([F:29])([F:28])[CH2:24][CH2:25][CH:26]=O.[CH3:30][C:31]([CH3:35])([CH3:34])[C:32]#[CH:33]>O.[Au](Br)(Br)Br>[CH3:30][C:31]([CH3:35])([CH3:34])[C:32]#[C:33][C@@H:26]([N:10]1[CH2:11][CH2:12][CH2:13][C@H:14]([CH2:15][C:16]([O:18][CH3:19])=[O:17])[C@H:9]1[C:6]1[CH:5]=[CH:4][C:3]([C:2]([F:20])([F:1])[F:21])=[CH:8][CH:7]=1)[CH2:25][CH2:24][C:23]([F:29])([F:28])[F:22]

Komponenten

6

Edukt 3

HCID 135123,3-Dimethyl-1-butyneHCID 27770834,4,4-TrifluorobutanalHCID 86639343methyl {(2S,3R)-2-[4-(trifluoromethyl)phenyl]piperidin-3-yl}acetate

Produkt 1

HCID 59201268methyl {(2S,3R)-1-[(1S)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pent-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-3-yl}acetate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 82525Gold tribromideKatalysatorHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A solution of methyl {(2S,3R)-2-[4-(trifluoromethyl)phenyl]piperidin-3-yl}acetate (2.1 g, 7.0 mmol), 4,4,4-trifluorobutanal (1.76 g, 13.9 mmol) and gold(III) bromide (0.3 g, 0.7 mmol) in water (50 mL) was degassed with nitrogen for 1.5 hours. To this solution was added 3,3-dimethylbut-1-yne (4.3 mL, 34.8 mmol) and the reaction was sealed and heated to 70° C. for 16 hours. The reaction was partitioned between water and ethyl acetate. The organics were dried over sodium sulfate, filtered and evaporated in vacuo. Purification by flash column chromatography (3% ethyl acetate/hexanes) gave methyl {(2S,3R)-1-[(1S)-4,4-dimethyl-1-(3,3,3-trifluoropropyl)pent-2-yn-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-3-yl}acetate as a clear oil. LC/MS (EIMS, M+H)=492.1.

Aufarbeitung

  1. customthe reaction was sealed
  2. customThe reaction was partitioned between water and ethyl acetate
  3. dry with materialThe organics were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customPurification by flash column chromatography (3% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-52be82cdff384863831e4856cbc53d86
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389547B2

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