Water → HCID 86657789, compound

HRID 401925Notes

Reaction equation

HRID 401925 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][O:15][C:16]2[N:17]=[N:18][C:19]([CH2:35][CH2:36][CH2:37][CH3:38])=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([O:28][CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)=[CH:24][CH:23]=3)[CH:21]=2)[C@H:10]([OH:39])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:42]I.O>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][O:15][C:16]2[N:17]=[N:18][C:19]([CH2:35][CH2:36][CH2:37][CH3:38])=[C:20]([C:22]3[CH:23]=[CH:24][C:25]([O:28][CH:29]4[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]4)=[CH:26][CH:27]=3)[CH:21]=2)[C@H:10]([O:39][CH3:42])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86657788HCID 86657788, compound

Product 1

HCID 86657789HCID 86657789, compoundYield 78.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of (±)-cis-4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.46 mmol, 0.25 g) in anhydrous DMF (1.5 mL) was added sodium hydride (60% dispersion in mineral oil) (0.92 mmol, 0.037 g) and continued stirring for 15 min. The reaction mixture was cooled to 0° C. using an ice bath. To this was added methyl iodide (0.57 mmol, 0.035 mL) and the reaction was stirred for 12 hours coming to room temperature. The reaction was poured into a mixture of water (5 mL) and ethyl acetate (5 mL). The mixture was shaken and separated. The ethyl acetate layer was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified on 24 g SiO2 cartridge using a gradient of ethyl acetate/hexanes to give (±)-cis-4-[6-butyl-5-(4-cyclohexyloxy-phenyl)-pyridazin-3-yloxymethyl]-3-methoxy-piperidine-1-carboxylic acid tert-butyl ester (0.20 g).

Workup

  1. stirringthe reaction was stirred for 12 hours
  2. customcoming to room temperature
  3. stirringThe mixture was shaken
  4. customseparated
  5. washThe ethyl acetate layer was washed with brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified on 24 g SiO2 cartridge

Sources & evidence

ORD record
ord-2516982c52b041dfaa533a40fa0392cf
Source dataset
uspto-grants-2014_06
Patent number
US08741900B2

Reaction notes

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