Propargyl bromide → 1-Methoxy-4-{prop-2-ynyloxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

HRID 1473772Notes

Reaction equation

HRID 1473772 reaction equation
[CH3:1][O:2][C:3]([C:5]1([N:13]([OH:26])[C:14](=[O:25])[CH2:15][C:16]2[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[CH:18][C:17]=2[CH3:24])[CH2:10][CH2:9][N:8]([O:11][CH3:12])[CH2:7][CH2:6]1)=[O:4].[H-].[Na+].[CH2:29](Br)[C:30]#[CH:31]>O1CCCC1>[CH3:1][O:2][C:3]([C:5]1([N:13]([O:26][CH2:31][C:30]#[CH:29])[C:14](=[O:25])[CH2:15][C:16]2[C:17]([CH3:24])=[CH:18][C:19]([CH3:23])=[CH:20][C:21]=2[CH3:22])[CH2:6][CH2:7][N:8]([O:11][CH3:12])[CH2:9][CH2:10]1)=[O:4]

Participants

5

Reactant 3

HCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 584280024-{Hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester

Product 1

HCID 584280801-Methoxy-4-{prop-2-ynyloxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-{hydroxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-1-methoxy-piperidine-4-carboxylic acid methyl ester (compound P3ii.3 obtained in analogy to preparation example 11, step 4) (500 mg, 1.37 mmol) in tetrahydrofuran (3 ml) at 0° C. was added sodium hydride (66 mg, 55% w/w dispersion in mineral oil, 1.51 mmol) in 2 portions. The reaction mixture was stirred at 0° C. for one hour, treated with propargyl bromide (202 mg, 1.65 mmol) dropwise, and further stirred at room temperature overnight. The reaction mixture was evaporated, diluted with ethyl acetate and filtered to remove salts. The filtrate was washed twice with brine, dried over sodium sulfate and concentrated. The oily residue was purified by chromatography on silica gel (ethyl acetate/hexane 1:2). Yield: 321 mg of 1-methoxy-4-{prop-2-ynyloxy-[2-(2,4,6-trimethyl-phenyl)-acetyl]-amino}-piperidine-4-carboxylic acid methyl ester (compound P3ii.4) as a colorless gum.

Workup

  1. stirringfurther stirred at room temperature overnight
  2. customThe reaction mixture was evaporated
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered
  5. customto remove salts
  6. washThe filtrate was washed twice with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated
  9. customThe oily residue was purified by chromatography on silica gel (ethyl acetate/hexane 1:2)

Sources & evidence

ORD record
ord-09e42d57c8194d6cbda8295191c4c977
Source dataset
uspto-grants-2015_04
Patent number
US09018135B2

Reaction notes

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