Ammonium Chloride → 1,1-Dimethylethyl 4-hydroxy-4-(3-trimethylsilyloxypropynyl)-1-piperidinecarboxylate

HRID 747004Notes

Reaction equation

HRID 747004 reaction equation
[CH3:1][Si:2]([CH3:8])([CH3:7])[O:3][CH2:4][C:5]#[CH:6].C([Mg]Br)C.[O:13]=[C:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.[Cl-].[NH4+]>O1CCCC1.C(OCC)(=O)C.O>[OH:13][C:14]1([C:6]#[C:5][CH2:4][O:3][Si:2]([CH3:8])([CH3:7])[CH3:1])[CH2:15][CH2:16][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:18][CH2:19]1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 79696Silane, trimethyl(2-propyn-1-yloxy)-HCID 735900tert-Butyl 4-oxopiperidine-1-carboxylateHCID 178418443HCID 178418443, compound

Product 1

HCID 219551731,1-Dimethylethyl 4-hydroxy-4-(3-trimethylsilyloxypropynyl)-1-piperidinecarboxylateYield 100%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Trimethyl(2-propynyloxy)silane (11.54 ml, 9.62 g, 75 mmol) was added dropwise to a stirred, cooled (−5° C.) solution of ethyl magnesium bromide (1M in tetrahydrofuran, 75 ml, 75 mmol) in tetrahydrofuran (150 ml), maintaining the internal temperature below 0° C. The mixture was stirred at 0° C. for 30 minutes, then at room temperature for 90 minutes. The mixture was cooled to −5° C. and 1,1-dimethylethyl 4-oxo-1-piperidinecarboxylate (15.0 g, 75 mmol) was added slowly, maintaining the internal temperature below 0° C. The mixture was stirred at 0° C. for 3 hours then at room temperature for 96 hours. Saturated aqueous ammonium chloride (300 ml), water (100 ml) and ethyl acetate (300 ml) were added and the layers were separated. The aqueous layer was extracted with ethyl acetate (200 ml) and the combined organic fractions were dried (MgSO4) and the solvent was evaporated under reduced pressure to give the title compound (24.4 g, 100%).

Workup

  1. temperaturemaintaining the internal temperature below 0° C
  2. waitat room temperature for 90 minutes
  3. temperatureThe mixture was cooled to −5° C.
  4. temperaturemaintaining the internal temperature below 0° C
  5. stirringThe mixture was stirred at 0° C. for 3 hours
  6. waitat room temperature for 96 hours
  7. customthe layers were separated
  8. extractionThe aqueous layer was extracted with ethyl acetate (200 ml)
  9. dry with materialthe combined organic fractions were dried (MgSO4)
  10. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-74180a164a7b46a98b0fc0f0d790d7ad
Source dataset
uspto-grants-2008_07
Patent number
US07393858B2

Reaction notes

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