Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Hydrochloric Acid | HCID 313 | — |
| Reactant | Triethylamine | HCID 8471 | — |
| Reactant | Methanesulfonyl chloride | HCID 31297 | — |
| Reactant | 1,8-Diazabicyclo(5.4.0)undec-7-ene | HCID 81184 | — |
| Reactant | HCID 86592519 | HCID 86592519 | — |
| Catalyst | 4-(Dimethylamino)pyridine | HCID 14284 | — |
| Solvent | Dichloromethane | HCID 6344 | — |
| Product | HCID 86592520 | HCID 86592520 | 15% |
| Product | HCID 86592521 | HCID 86592521 | 68% |
Reaction Steps
To a solution of 1-allyl 4-tert-butyl (2R)-5-hydroxy-2-[(methoxymethoxy)methyl]-1,4-piperidinedicarboxylate (1.22 g, 3.4 mmol) in dichloromethane (9.4 ml) were added at −30° C. methanesulfonyl chloride (0.4 ml, 5.1 mmol), triethylamine (0.95 ml, 6.8 mmol) and 4-dimethylaminopyridine ((41.5 mg, 0.34 mmol), and the mixture was stirred 0° C. for 40 minutes. The reaction mixture was poured into diluted hydrochloric acid and the mixture was extracted three times with chloroform. The organic layer was washed with a saturated aqueous sodium chloride, and dried over magnesium sulfate. The organic solvent was removed under reduced pressure, and the residue was dissolved in toluene (5 ml) and dichloromethane (10 ml). The mixture was cooled to 0° C. and thereto was added DBU (0.76 ml, 5.1 mmol). The mixture was raised to room temperature and was stirred accurately for 20 minutes. The reaction mixture was poured into diluted hydrochloric acid and extracted three times with ethyl acetate. The organic layer was washed with water and then a saturated aqueous sodium chloride solution. The organic layer was dried over magnesium sulfate and the organic solvent was removed under reduced pressure. The residue was purified by silica gel (30 g) chromatography (Hexane/ethyl acetate: 2/1) to give 1-allyl 4-tert-butyl (2R)-2-[(methoxymethoxy)methyl]-5-[(methylsulfonyl)oxy]-1,4-piperidinedicarboxylate (0.24 g, 15%) and 1-allyl 4-tert-butyl (2R)-2-[(methoxymethoxy)methyl]-3,6-dihydro-1,4(2 H)-pyridinedicarboxylate (0.79 g, 68%).
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US07163936B2 |
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| Source dataset | uspto-grants-2007_01 |
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| ORD ID | ord-cabd0f84b1ed46779ffe7440e4f97456 |
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| Source note | uspto-grants-2007_01 |
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