2,2,2-Trifluoroethanol → HCID 66818419, compound

HRID 1754921Notes

Reaction equation

HRID 1754921 reaction equation
[H-].[Na+].[F:3][C:4]([F:8])([F:7])[CH2:5][OH:6].[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][C:19]([NH:24][C:25](=[O:34])[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([CH2:32]Cl)[CH:27]=2)([C:22]#[N:23])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>CN(C=O)C>[C:9]([O:13][C:14]([N:16]1[CH2:17][CH2:18][C:19]([C:22]#[N:23])([NH:24][C:25](=[O:34])[C:26]2[CH:31]=[CH:30][CH:29]=[C:28]([CH2:32][O:6][CH2:5][C:4]([F:8])([F:7])[F:3])[CH:27]=2)[CH2:20][CH2:21]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 66816128HCID 66816128, compound

Product 1

HCID 66818419HCID 66818419, compoundYield 52.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% oil suspension, 191 mg, 4.77 mmol) was added to a solution of 2,2,2-trifluoro-ethanol (347 μl, 4.77 mmol) and 4-(3-chloromethyl-benzoylamino)-4-cyano-piperidine-1-carboxylic acid tert-butyl ester (600 mg, 1.59 mmol) in DMF (8 ml) at 0° C. The mixture was stirred at room temperature overnight, and then quenched with water and diluted with ethyl acetate. The organic layer was sequentially washed with a saturated aqueous NaHCO3 solution, water (×2) and saturated brine, and then dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1→1/2) to give 4-cyano-4-[3-(2,2,2-trifluoro-ethoxymethyl)-benzoylamino]-piperidine-1-carboxylic acid tert-butyl ester as a white solid (366 mg, 52%).

Workup

  1. customquenched with water
  2. additiondiluted with ethyl acetate
  3. washThe organic layer was sequentially washed with a saturated aqueous NaHCO3 solution, water (×2) and saturated brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1→1/2)

Sources & evidence

ORD record
ord-133493588a29448592f2aebf52b4c8fa
Source dataset
uspto-grants-2015_10
Patent number
US09169254B2

Reaction notes

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