Water → HCID 131733085, compound

HRID 1518961Notes

Reaction equation

HRID 1518961 reaction equation
[H-].[Na+].[OH:3][C@@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C@H:5]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[CH3:23]I.O>CN(C=O)C>[CH3:23][O:3][C@@H:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C@H:5]1[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodide2×HCID 24758Sodium hydride2×HCID 58592902HCID 58592902, compound

Product 1

HCID 131733085HCID 131733085, compoundYield 101.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
22 °C

Procedure

Add sodium hydride (2.19 g, 54.75 mmol) in one portion to a solution of (−)trans-tert-butyl 4-hydroxy-3-phenyl-piperidine-1-carboxylate (11.8 g, 42.12 mmol) in DMF (168.5 mL) at 0° C. under a nitrogen atmosphere. Stir the mixture for 30 min and then add methyl iodide (3.15 mL, 50.54 mmol) dropwise. Stir the mixture at 0° C. for 1 minute and warm to 22° C. for 1 hour. Add additional sodium hydride (303 mg, 12.6 mmol), stir for 15 min, and then add methyl iodide (0.52 mL, 8.4 mmol) slowly. Stir the mixture at 22° C. for 1 hour, cool to 0° C. for 1 hour and add water (118 mL) carefully. Filter the resulting suspension, rinse the solid with water and dry the solid in the vacuum oven (45° C., 60 mbar) to obtain the title compound as a white solid (12.5 g, 99%). MS (m/z): 192 (M-Boc+1), 236 (M-tBu+1).

Workup

  1. stirringStir the mixture at 0° C. for 1 minute
  2. stirringstir for 15 min
  3. stirringStir the mixture at 22° C. for 1 hour
  4. temperaturecool to 0° C. for 1 hour
  5. filtrationFilter the resulting suspension
  6. washrinse the solid with water
  7. customdry the solid in the vacuum oven (45° C., 60 mbar)

Sources & evidence

ORD record
ord-bb7e9464a0604f329c9ed20b5a4f6db5
Source dataset
uspto-grants-2015_07
Patent number
US09073856B2

Reaction notes

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