Diisopropylethylamine → (R)-5-(5-bromo-2-fluorophenyl)-4-(2,4-dimethoxybenzyl)-5-methylthiomorpholin-3-one
Reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C@:8]([NH:16][CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=2[O:26][CH3:27])([CH3:15])[CH2:9][S:10][CH2:11][C:12](O)=[O:13])[CH:7]=1.C(N(CC)C(C)C)(C)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:28])=[C:6]([C@@:8]2([CH3:15])[N:16]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][C:19]=3[O:26][CH3:27])[C:12](=[O:13])[CH2:11][S:10][CH2:9]2)[CH:7]=1Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of (R)-2-(2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino) propylthio)acetic acid (3.3 g, 6.99 mmol, Eq: 1.00) and N,N-diisopropylethylamine (2.71 g, 3.66 ml, 21.0 mmol, Eq: 3.0) in ethyl acetate (194 ml) was added at 23° C. 1-propanephosphonic acid cyclic anhydride (50% solution in ethyl acetate) (6.67 g, 6.23 ml, 10.5 mmol, Eq: 1.5) and the colourless reaction solution was stirred at 23° C. for 2 hours. The reaction mixture was washed with sat NaHCO3-sol., water and brine. The organic layer was dried over Na2SO4, filtered and evaporated to give the nearly pure (R)-5-(5-bromo-2-fluorophenyl)-4-(2,4-dimethoxybenzyl)-5-methylthiomorpholin-3-one (2.95 g, 6.49 mmol, 92.9% yield) as a colourless oil, which crystallized in the fridge and was used without further purification. MS (ISP): m/z=454.0 [M+H]+ and 456.1 [M+2+H]+.
Workup
- washThe reaction mixture was washed with sat NaHCO3-sol
- dry with materialThe organic layer was dried over Na2SO4
- filtrationfiltered
- customevaporated
Sources & evidence
- ORD record
- ord-4b44720e5ab04c7b942617b45e7c3301
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09273042B2
Reaction notes
Loading…