Water → (2s,3s)-n-Cyclopropyl-3-(tert-butoxycarbonyl)-amino-2-hydroxyhexanoic acid amide
Reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[C:5]([O:9][C:10](N[C@@H](CCC)[C@H](O)C(O)=O)=[O:11])([CH3:8])([CH3:7])[CH3:6].[CH:22]1[CH:27]=[C:26]2N=N[N:30](O)[C:25]2=[CH:24][CH:23]=1.[OH2:32].CCN=C=NCCCN(C)C.Cl.C([O-])(O)=O.[Na+].[OH2:50]>C1COCC1.C(OCC)(=O)C>[CH:1]1([NH:4][C:24](=[O:50])[C@@:25]([NH2:30])([OH:32])[C@@H:26]([C:10]([O:9][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:11])[CH2:27][CH2:22][CH3:23])[CH2:3][CH2:2]1Participants
Reactant 6
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 40 °C
Procedure
Cyclopropylamine (13.9 g, 242.6 mmol) was dropwise added to a mixed solution of ethyl acetate (250 g)/THF (250 g)=1/1 and (2S,3S)-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid (50.0 g, 202.2 mmol). The mixture was cooled by ice. A mixed solution of HOBt monohydrate (32.5, 212.3 mmol), EDC hydrochloride (42.6 g, 222.4 mmol) and water (43 g) was dropwise added thereto, and the mixture was stirred for 14 hours with cooling by ice. Next, 5% NaHCO3 aqueous solution (250 g) was added thereto, and the mixture was heated up to 40° C. Then, the aqueous layer was removed, and the organic-layer was washed twice with 5% NaHCO3 aqueous solution (250 g) at 40° C. and finally washed with water (250 g), to obtain a solution of (2S,3S)—N-cyclopropyl-3-(tert-butoxycarbonyl)-amino-2-hydroxyhexanoic acid amide (reaction yield: 95 mol %, extraction yield: 89 mol %, chemical purity: 96.9 area %).
Workup
- temperatureThe mixture was cooled by ice
- temperaturewith cooling by ice
- customThen, the aqueous layer was removed
- washthe organic-layer was washed twice with 5% NaHCO3 aqueous solution (250 g) at 40° C.
- washfinally washed with water (250 g)
Sources & evidence
- ORD record
- ord-2726c1ef860f413f90fa8707449f5771
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08183413B2
Reaction notes
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