Water → methyl (3R)-3-[(2-chloro-5-fluoropyrimidin-4-yl)amino]-4,4-dimethylpentanoate
Reaction equation
[Cl-].[CH3:2][O:3][C:4](=[O:12])[CH2:5][C@@H:6]([NH3+:11])[C:7]([CH3:10])([CH3:9])[CH3:8].[Cl:13][C:14]1[N:19]=[C:18](Cl)[C:17]([F:21])=[CH:16][N:15]=1.C(N(CC)CC)C.O>O1CCCC1.CCO.ClCCl>[Cl:13][C:14]1[N:19]=[C:18]([NH:11][C@@H:6]([C:7]([CH3:8])([CH3:9])[CH3:10])[CH2:5][C:4]([O:3][CH3:2])=[O:12])[C:17]([F:21])=[CH:16][N:15]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 55 °C
Procedure
(R)-1-methoxy-4,4-dimethyl-1-oxopentan-3-aminium chloride, 5a, (37 g, 189 mmol) was dissolved in a mixture of tetrahydrofuran (667 mL) and EtOH (74 mL). The solution was cooled in an ice bath. 2,4-dichloro-5-fluoro-pyrimidine (35 g, 208 mmol) was added, followed by the dropwise addition of triethylamine (85 mL, 606 mmol). The reaction mixture was heated at 55° C. for 17 h. The reaction mixture was then cooled to room temperature after which water (625 mL) and dichloromethane (625 mL) were added. The phases were separated and the aqueous layer was washed with dichloromethane (625 mL). The organic layers were combined and washed with brine. The solvents were removed and the residue was purified on silica gel (EtOAc/Hexanes): LCMS Gradient 10-90%, 0.1% formic acid, 5 min, C18/ACN, RT=3.10 minutes (M+H) 291.02.
Workup
- temperatureThe solution was cooled in an ice bath
- additionwere added
- customThe phases were separated
- washthe aqueous layer was washed with dichloromethane (625 mL)
- washwashed with brine
- customThe solvents were removed
- customthe residue was purified on silica gel (EtOAc/Hexanes)
- customLCMS Gradient 10-90%, 0.1% formic acid, 5 min
Sources & evidence
- ORD record
- ord-bfb7b7f7271a42b5884edcf7921a1431
- Source dataset
- uspto-grants-2015_06
- Patent number
- US09051319B2
Reaction notes
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