(RS)-4-(3-Bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine → (S)-(+)-4-(3-bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8]2([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([F:23])[F:22])=[C:16]([CH3:24])[CH:15]=3)[CH2:12][O:11][C:10]([NH2:13])=[N:9]2)[CH:5]=[CH:6][CH:7]=1>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([C@@:8]2([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH:21]([F:22])[F:23])=[C:16]([CH3:24])[CH:15]=3)[CH2:12][O:11][C:10]([NH2:13])=[N:9]2)[CH:5]=[CH:6][CH:7]=1Participants
Reactant 1
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 1.95 g of (RS)-4-(3-bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine (Building Block S) in dichloromethane was divided in 200 mg aliquots which were separated on chiral HPLC (Chiralpak AD) using a 92:8-mixture of heptane and isopropanol as the eluent. The fractions showing e.e. values in the range of 99.7% to 98.4% of the first eluting enantiomer were combined to give 994 mg of the (S)-(+)-4-(3-bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine as a colourless oil which crystallised on standing. The later eluting enantiomer (R)-(−)-4-(3-bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-4,5-dihydro-oxazol-2-ylamine was isolated to give 628 mg (96.8% e.e.) as a colourless oil which crystallised on standing. In addition, a fraction (137 mg) consisting of both isomers was also obtained.
Workup
- customwere separated on chiral HPLC (Chiralpak AD)
Sources & evidence
- ORD record
- ord-d8f460ed8de74b668d6cf2a016e8ee6b
- Source dataset
- uspto-grants-2011_08
- Patent number
- US07989449B2
Reaction notes
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