Cesium fluoride → HCID 86708250, compound

HRID 529340Notes

Reaction equation

HRID 529340 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[F-].[Cs+].[F:14][C:15]([F:37])([F:36])[C:16]([N:18]([C@@H:27]1[CH2:29][C@H:28]1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:19][CH2:20][CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1)=[O:17].FC(F)(F)C([O-])=O>CN(C)C(=O)C.O>[F:37][C:15]([F:14])([F:36])[C:16]([N:18]([CH2:19][CH2:20][CH:21]1[CH2:26][CH2:25][N:24]([C:2]2[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=2)[CH2:23][CH2:22]1)[C@@H:27]1[CH2:29][C@H:28]1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:17]

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 84468TrifluoroacetateHCID 13349623Methyl 6-bromopyridine-3-carboxylateHCID 86708247HCID 86708247, compound

Product 1

HCID 86708250HCID 86708250, compoundYield 27.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 6-bromonicotinate, 13 (0.476 g, 2.206 mmol) and CsF (2.68 g, 17.64 mmol) were added to a stirred solution of 2,2,2-trifluoro-N-((trans)-2-phenylcyclopropyl)-N-(2-(piperidin-4-yl)ethyl)acetamide, trifluoroacetate (1 g, 2.206 mmol) in N,N-dimethylacetamide (10 mL) in a Microwave vial. The reaction vessel was sealed and heated in CEM Discover to 100° C. for 45 min under microwave conditions. Reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (2×30 mL). The combined organic layer was washed with water (2×30 mL), brine (1×50 mL), filtered and dried over Na2SO4 and concentrated under reduced pressure to afford crude product. The crude product was purified by column chromatography using 100-200 mesh silica gel, by eluting with 30% ethyl acetate in pet-ether to afford methyl 6-(4-(2-(2,2,2-trifluoro-N-((trans)-2-phenylcyclopropyl)acetamido)ethyl)piperidin-1-yl)nicotinate (500 mg, 27.3% yield) as yellow gum. LCMS (ES) m/e 476.14 (M+H)+.

Workup

  1. customThe reaction vessel was sealed
  2. customReaction mixture
  3. extractionextracted with ethyl acetate (2×30 mL)
  4. washThe combined organic layer was washed with water (2×30 mL), brine (1×50 mL)
  5. filtrationfiltered
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude product
  9. customThe crude product was purified by column chromatography
  10. washby eluting with 30% ethyl acetate in pet-ether

Sources & evidence

ORD record
ord-c6bda853a3554ffc8d7c424269fac64e
Source dataset
uspto-grants-2016_05
Patent number
US09346840B2

Reaction notes

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