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Cyclopropylamine → tert-Butyl ((2S,3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)carbamate

HRID 1928702
Notes
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Reaction equation

HRID 1928702 reaction equation
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[C:5]([O:9][C:10]([NH:12][C@@H:13]([CH2:19][CH2:20][CH3:21])[C@H:14]([OH:18])[C:15](O)=[O:16])=[O:11])([CH3:8])([CH3:7])[CH3:6].C1C=C2N=NN(O)C2=CC=1.O.CCN=C=NCCCN(C)C.Cl.C([O-])(O)=O.[Na+]>O.C(OCC)(=O)C>[CH:1]1([NH:4][C:15](=[O:16])[C@@H:14]([OH:18])[C@@H:13]([NH:12][C:10]([O:9][C:5]([CH3:8])([CH3:7])[CH3:6])=[O:11])[CH2:19][CH2:20][CH3:21])[CH2:3][CH2:2]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 5

HCID 69828CyclopropylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 29928234(2S,3S)-3-tert-butoxycarbonylamino-2-hydroxyhexanoic acid

Product 1

HCID 68950941
tert-Butyl ((2S,3S)-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

Cyclopropylamine (1.99 g, 34.94 mmol) was dropwise added to a mixed solution of (2S,3S)-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid (7.2 g, 29.12 mmol), ethyl acetate (144 g) and water (7.2 g). The mixture was cooled by ice. HOBt monohydrate (4.68 g, 30.58 mmol) and EDC hydrochloride (6.14 g, 32.03 mmol) were added thereto, and the mixture was stirred with cooling by ice for 22 hours. Next, 5% NaHCO3 aqueous solution (72 g) was added thereto, and the mixture was heated up to 40° C. Then, the aqueous layer was removed. The organic layer was washed twice with 5% NaHCO3 aqueous solution (72 g) at 40° C., and finally the organic layer was washed with water (72 g), to obtain an ethyl acetate solution of (2S,3S)—N-cyclopropyl-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid amide (yield: 90 mol %, chemical purity: 96.1 area %, optical purity: 99.3% ee). The obtained organic layer (140.2 g) was concentrated under reduced pressure to be 62.5 g, using a rotary evaporator. The obtained slurry was heated up to 60° C. so as to dissolve the contents, and then cooled to 51° C. Seed crystals of (2S,3S)—N-cyclopropyl-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid amide (2 mg) were added to the solution. As a result, crystals were gradually precipitated. The mixture was aged at the same temperature for 1 hour, and then was cooled to 2° C., taking about 5 hours. The precipitated crystals were separated and dried to obtain (2S,3S)—N-cyclopropyl-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid amide (6.45 g, isolation yield: 78 mol %, chemical purity: 100.0 area %, optical purity: 100% ee).

Workup

  1. temperatureThe mixture was cooled by ice
  2. temperaturewith cooling by ice for 22 hours
  3. customThen, the aqueous layer was removed
  4. washThe organic layer was washed twice with 5% NaHCO3 aqueous solution (72 g) at 40° C.
  5. washfinally the organic layer was washed with water (72 g)

Sources & evidence

ORD record
ord-be802114fcde4f149dacb3b26a13059b
Source dataset
uspto-grants-2012_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08183413B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes