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 1942312노트

반응식

HRID 1942312 반응식
[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]

참가 물질

6

반응물 3

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

생성물 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

시약·촉매·용매 2

HCID 82525Gold tribromide촉매HCID 962Water용매

반응 조건

온도
70 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-52be82cdff384863831e4856cbc53d86
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389547B2

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