HOAt → [(S)-2-ethoxy-1-(4-fluoro-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester

HRID 242964Notes

Reaction equation

[F:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]([NH2:8])=[CH:6][CH:7]=1.[C:16]([O:20][C:21]([NH:23][C@@H:24]([CH2:28][O:29][CH2:30][CH3:31])[C:25](O)=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl>[C:16]([O:20][C:21](=[O:22])[NH:23][C@H:24]([C:25](=[O:26])[NH:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=1[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:28][O:29][CH2:30][CH3:31])([CH3:17])([CH3:18])[CH3:19]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-fluoro-N2-phenylbenzene-1,2-diamine (562 mg, 2.8 mmol) in DCM (18 mL) at 0° C. were added (S)-2-tertbutoxycarbonylamino-3-ethoxypropionic acid (720 mg, 3.1 mmol), HOAt (0.420 g, 3.1 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.59 g, 3.1 mmol) and the resulting mixture stirred at 0° C. for 1 h. The reaction mixture was partitioned between DCM and a saturated aqueous solution of NaHCO3. The organic fraction was washed with brine, dried (MgSO4), concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane) to afford [(S)-2-ethoxy-1-(4-fluoro-2-phenylaminophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester (770 mg, 66%). LCMS (Method B): RT 3.87 min [M+H]+ 418.3

Workup

customThe reaction mixture was partitioned between DCM
washThe organic fraction was washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-a007e52653184b1796d0e36cff56250a
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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