4-Methylmorpholine → (S)-2-Boc-amino-3-(3,5-difluorophenyl)propan-1-OL
Reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>COCCOC.O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH2:10][OH:11])[CH2:13][C:14]1[CH:19]=[C:18]([F:20])[CH:17]=[C:16]([F:21])[CH:15]=1)([CH3:2])([CH3:4])[CH3:3]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- -20 °C
Procedure
Dissolve commercially available 2-(S)-tert-butoxycarbonylamino-3-(3,5-difluorophenyl)propionic acid (5.995 g, 19.9 mmol) in ethylene glycol dimethyl ether (20 mL) and cool −20° C. Add 4-methylmorpholine (2.4 mL, 21.89 mmol) and stir 5 min, then add isobutyl chloroformate (2.9 mL, 21.89 mmol) dropwise and stir 5 min. Filter into −15° C. cooled flask with course frit, rinse with cold ethylene glycol dimethyl ether. Add sodium borohydride (1.129 g, 29.85 mmol) in water (9 mL) followed by water (500 mL), then warm to room temperature. Filter and dissolve solid in dichloromethane. Wash with saturated aqueous sodium chloride, dry (magnesium sulfate) and concentrate to give the title compound as a solid (4.57 g, 80%).
Workup
- filtrationFilter into −15° C.
- temperaturecooled flask with course frit
- washrinse with cold ethylene glycol dimethyl ether
- temperaturewarm to room temperature
- filtrationFilter
- dissolutiondissolve solid in dichloromethane
- washWash with saturated aqueous sodium chloride
- dry with materialdry (magnesium sulfate)
- concentrationconcentrate
Sources & evidence
- ORD record
- ord-21d736e61fd143619af62201a24be08f
- Source dataset
- uspto-grants-2009_11
- Patent number
- US07618978B2
Reaction notes
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