Hydrochloric Acid → (3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-aminium chloride
Reaction equation
[CH2:1]([C@@H:8]1[C@@H:16]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])[C@H:15]([CH3:22])[O:14][C:13](=[O:23])[C@@H:12]([N:24](C(OC(C)(C)C)=O)C(=O)OC(C)(C)C)[CH2:11][O:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:39]>C(Cl)Cl>[Cl-:39].[CH2:1]([C@@H:8]1[C@@H:16]([O:17][CH2:18][CH:19]([CH3:20])[CH3:21])[C@H:15]([CH3:22])[O:14][C:13](=[O:23])[C@@H:12]([NH3+:24])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of tert-butyl N-[(3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-yl]-N-tert-butoxycarbonylcarbamate (3.586 g, 6.69 mmol) in CH2Cl2 (33 mL) was added HCl (4M in dioxane; 33.5 ml, 134 mmol, 20 equiv). This solution was stirred for 1 h and concentrated to furnish (3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-aminium chloride as a white solid. The solid was suspended in CH2Cl2 (66 mL), and N-methylmorpholine (4.42 ml, 40.2 mmol, 6.00 equiv) was added, causing dissolution of the solid. To this solution were added 3-hydroxy-4-methoxypicolinic acid (1.70 g, 10.0 mmol, 1.50 equiv) and HATU (4.07 g, 10.71 mmol, 1.60 equiv). The resulting suspension was stirred at room temperature for 20 h, concentrated, and purified by automated silica gel column chromatography (2-12% acetone in CH2Cl2) to yield N-((3S,7S,8R,9S)-7-benzyl-8-isobutoxy-9-methyl-2-oxo-1,5-dioxonan-3-yl)-3-hydroxy-4-methoxypicolinamide (2.08 g, 63.9%) as a yellow oil.
Workup
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-3166d465312742969fd5e8da89035f15
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08835462B2
Reaction notes
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