Toluene → 1,1-Dimethylethyl 4-(2-propyn-1-yloxy)-1-piperidinecarboxylate

HRID 930330Notes

Reaction equation

HRID 930330 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[H-].[Na+].[CH2:17](Br)[C:18]#[CH:19].C1(C)C=CC=CC=1>C1COCC1>[CH2:19]([O:14][CH:11]1[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]1)[C:18]#[CH:17]

Participants

6

Reactant 4

HCID 1140TolueneHCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylate

Product 1

HCID 496579171,1-Dimethylethyl 4-(2-propyn-1-yloxy)-1-piperidinecarboxylateYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a RT solution of 1-boc-4-hydroxypiperidine (1.20 g, 5.96 mmol) in THF (20 mL) was added sodium hydride dispersion in mineral oil (0.440 g, 11.00 mmol, 57%), in portions, as a solid. After 30 min propargyl bromide, 80% solution in toluene (1.80 mL, 16.16 mmol) was added dropwise via syringe and the reaction was allowed to stir for 2 h. The reaction was cooled to 0° C., quenched with water and extracted with EtOAc (3×). The combined organic layers were washed with brine, evaporated onto silica gel and purified by flash chromatography (Isco (80 gram)) eluting with (EtOAc):hexanes (0:1→1:1) to give the titled compound as a colorless oil (861 mg, 60%). MS m/z=183.9 [M−tBu]+. Calculated for C9H12NO3: 182

Workup

  1. customquenched with water
  2. extractionextracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. customevaporated onto silica gel
  5. custompurified by flash chromatography (Isco (80 gram))
  6. washeluting with (EtOAc)

Sources & evidence

ORD record
ord-ff4d5292d20647c09ab225ff89004c65
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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