Bromoacetonitrile → (R)-tert-butyl 2-((S)-(3-chlorophenyl)(cyanomethoxy)methyl)morpholine-4-carboxylate
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([OH:22])[C@@H:9]2[O:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:26][C:27]#[N:28]>CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:22][CH2:26][C:27]#[N:28])[C@@H:9]2[O:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of (R)-tert-butyl 2-((S)-(3-chlorophenyl)(hydroxy)methyl)morpholine-4-carboxylate (1.3 g, 3.98 mmol) in MeCN (20 mL), NaH (230 mg, 9.55 mmol) was added at 0° C. The mixture was stirred for 1 h at rt. The mixture was cooled to −40° C., and bromoacetonitrile (1.14 g, 9.55 mmol) was added in portions. The mixture was stirred for 0.5 h at −20° C. The solution was evaporated and H2O (50 mL) was added. 1N aq HCl was added and the mixture was extracted with CH2Cl2. The organic layer was washed with aq NaHCO3 and brine, dried over Na2SO4 and concentrated. The crude product was used directly in the next step.
Workup
- temperatureThe mixture was cooled to −40° C.
- stirringThe mixture was stirred for 0.5 h at −20° C
- customThe solution was evaporated
- additionH2O (50 mL) was added
- addition1N aq HCl was added
- extractionthe mixture was extracted with CH2Cl2
- washThe organic layer was washed with aq NaHCO3 and brine
- dry with materialdried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-edc1c239f44f40e5887eef213af0b5b1
- Source dataset
- uspto-grants-2011_01
- Patent number
- US07872028B2
Reaction notes
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