Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Water | HCID 962 | — |
| Reactant | Methyl iodide | HCID 6328 | — |
| Reactant | Sodium hydride | HCID 24758 | — |
| Reactant | HCID 86657788 | HCID 86657788 | — |
| Solvent | Dimethylformamide | HCID 6228 | — |
| Solvent | Ethyl Acetate | HCID 8857 | — |
| Product | HCID 86657789 | HCID 86657789 | 78.5% |
Reaction Steps
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).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US08741900B2 |
|---|
| Source dataset | uspto-grants-2014_06 |
|---|
| ORD ID | ord-2516982c52b041dfaa533a40fa0392cf |
|---|
| Source note | uspto-grants-2014_06 |
|---|