Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Ammonium Chloride | HCID 25517 | — |
| Reactant | p-Toluenesulfonic acid monohydrate | HCID 521998 | — |
| Reactant | 4-[4-(Trifluoromethoxy)phenoxy]piperidine | HCID 16115439 | — |
| Reactant | Sodium t-butoxide | HCID 23676156 | — |
| Reactant | HCID 71059491 | HCID 71059491 | — |
| Catalyst | Bis(dibenzylideneacetone)palladium | HCID 9811564 | — |
| Catalyst | Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane | HCID 11618717 | — |
| Solvent | Toluene | HCID 1140 | — |
| Product | HCID 86674236 | HCID 86674236 | 85.7% |
Reaction Steps
(R)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diol (20.0 kg, 76.6 mol), 4-[4-(trifluoromethoxy)phenoxy]piperidine (22.0 kg, 84.3 mol), tris(dibenzylideneacetone)dipalladium (0) (175 g, 0.19 mol), 2-di-tert-butylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl (195 g, 0.46 mol), sodium tert-butoxide (8.46 kg, 88.0 mol), and toluene (240 ml) were mixed, followed by stirring under an argon atmosphere at 70° C. for 3 hours. After cooling, an ammonium chloride aqueous solution was added to the reaction mixture, followed by extraction with toluene. Isopropanol was flowed therein, and p-toluenesulfonic acid monohydrate (16.0 kg, 84.1 mol) was added thereto, followed by stirring. The precipitated crystals thus obtained were collected by filtration and dried, obtaining 40.3 kg of (R)-2-methyl-3-(4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenoxy)propane-1,2-diol p-toluenesulfonic acid salt (yield: 85.7%).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
|---|
| Patent number | US08598358B2 |
|---|
| Source dataset | uspto-grants-2013_12 |
|---|
| ORD ID | ord-d8063b5e244646699340c273c205d66d |
|---|
| Source note | uspto-grants-2013_12 |
|---|
