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 1942312Notes

Reaction equation

HRID 1942312 reaction equation
[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]

Participants

6

Reactant 3

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

Product 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

Reagents, catalysts & solvents 2

HCID 82525Gold tribromideCatalystHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

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.

Workup

  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)

Sources & evidence

ORD record
ord-52be82cdff384863831e4856cbc53d86
Source dataset
uspto-grants-2013_03
Patent number
US08389547B2

Reaction notes

Loading…