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

HRID 1928704Notes

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.C1COCC1.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

Participants

Conditions

Temperature: 40 °C

Procedure

Cyclopropylamine (2.77 g, 48.53 mmol) was dropwise added to an ethyl acetate (108 g) solution of (2S,3S)-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid (10.0 g, 40.44 mmol). The mixture was cooled by ice. A mixed solution of HOBt monohydrate (1.86 g, 12.13 mmol)/THF (9.3 g)/water (1.9 g)=1/5/1 and a mixed solution of EDC hydrochloride (8.53 g, 44.48 mmol)/water (8.5 g)=1/1 were dropwise added in that order, and the mixture was stirred for 14 hours with cooling by ice. Next, 5% NaHCO3 aqueous solution (50 g) was added, and the mixture was heated up to 40° C. Then, the aqueous layer was removed. The organic layer was washed once with 5% NaHCO3 aqueous solution (50 g) at 40° C., and finally washed with water (50 g), to obtain a solution of (2S,3S)—N-cyclopropyl-3-(tert-butoxycarbonyl)amino-2-hydroxyhexanoic acid amide (reaction yield: 97 mol %, extraction yield: 98 mol %, chemical purity: 96.0 area %).

Workup

temperatureThe mixture was cooled by ice
temperaturewith cooling by ice
customThen, the aqueous layer was removed
washThe organic layer was washed once with 5% NaHCO3 aqueous solution (50 g) at 40° C.
washfinally washed with water (50 g)

Sources & evidence

ORD record: ord-9613e9bcc9404aec8b3ad9116b4c4df3
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08183413B2

Reaction notes

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