1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [(S)-1-(2-Benzylamino-4-fluorophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester

HRID 243118Notes

Reaction equation

[CH2:1]([NH:8][C:9]1[C:10]([NH2:16])=[CH:11][CH:12]=[C:13]([F:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:17]([O:21][C:22]([NH:24][C@@H:25]([CH3:29])[C:26](O)=[O:27])=[O:23])([CH3:20])([CH3:19])[CH3:18].C1C=NC2N(O)N=NC=2C=1.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:17]([O:21][C:22](=[O:23])[NH:24][C@H:25]([C:26](=[O:27])[NH:16][C:10]1[CH:11]=[CH:12][C:13]([F:15])=[CH:14][C:9]=1[NH:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH3:29])([CH3:18])([CH3:19])[CH3:20]

Participants

Conditions

Temperature: 0 °C

Procedure

N2-Benzyl-4-fluoro-benzene-1,2-diamine (1.2 g, 5.55 mmol) was dissolved in DCM (20 mL) and (S)-2-tert-butoxycarbonylaminopropionic acid (1.14 g, 6.0 mmol) and HOAt (0.82 g, 6.0 mmol) added. The reaction mixture was cooled to 0° C. and N-(3-dimethylaminopropyl)-N′ ethylcarbodiimide (1.15 g, 6.0 mmol) added. The resultant dark brown mixture was stirred at 0° C. for 1 h. The mixture was allowed to reach RT and was diluted with DCM (20 mL) and washed with 10% aqueous citric acid. The organic fraction was washed with brine (20 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a dark yellow gum, which solidified on standing (1.7 g, 79%). LCMS (Method B): RT 3.67 min [M+H]+ 388.1

Workup

customto reach RT
washwashed with 10% aqueous citric acid
washThe organic fraction was washed with brine (20 mL)
dry with materialdried (MgSO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by column chromatography (silica gel, gradient 0-50% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-4b54d28825a64809be3c0efa8ee97708
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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