Sulfuric Acid → (3S)-3-amino-1-methyl-3-[3-[4-[3-(trifluoromethoxy)phenyl]-2-pyridyl]prop-2-ynyl]pyrrolidin-2-one
Reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][C@@:4]([NH:27]C(=O)OC(C)(C)C)([CH2:7][C:8]#[C:9][C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:26])([F:25])[F:24])[CH:17]=3)[CH:13]=[CH:12][N:11]=2)[C:3]1=[O:35].OS(O)(=O)=O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C(OCC)(=O)C>[NH2:27][C@@:4]1([CH2:7][C:8]#[C:9][C:10]2[CH:15]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:26])([F:25])[F:24])[CH:17]=3)[CH:13]=[CH:12][N:11]=2)[CH2:5][CH2:6][N:2]([CH3:1])[C:3]1=[O:35]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
A solution of tert-butyl N-[(3S)-1-methyl-2-oxo-3-[3-[4-[3-(trifluoromethoxy)phenyl]-2-pyridyl]prop-2-ynyl]pyrrolidin-3-yl]carbamate (8.91 g, 18.19 mmol) (which may be prepared as described in Description 106) in 1,4-dioxane (70 mL) was cooled in an ice bath and treated dropwise with conc. H2SO4 (7.4 mL, 93.22 mmol). The mixture was allowed to reach room temperature and after 45 mins, the mixture was again cooled in an ice bath and treated cautiously with satd. aq. Na2CO3 solution (˜150 ml). The mixture was diluted with ethyl acetate (200 ml) and the product was extracted into ethyl acetate (2×150 ml). The combined organic extracts were dried (Na2SO4) and concentrated to give the title compound (D107) as an orange oil (6.88 g, 97%) consistent spectroscopically with that prepared by Method A.
Workup
- temperaturethe mixture was again cooled in an ice bath
- additiontreated cautiously with satd
- extractionthe product was extracted into ethyl acetate (2×150 ml)
- dry with materialThe combined organic extracts were dried (Na2SO4)
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-5a9f1083b1194bd5b250105321263baa
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09376436B2
Reaction notes
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