Dimethyl Sulfoxide → (2S,3S)-2-(tert-butoxycarbonylamino)-3-(5-cyano-2-nitrophenylamino)butanoic acid

HRID 1486082Notes

Reaction equation

[NH2:1][C@@H:2]([CH3:15])[C@H:3]([NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:4]([OH:6])=[O:5].CS(C)=O.F[C:21]1[CH:22]=[C:23]([CH:26]=[CH:27][C:28]=1[N+:29]([O-:31])=[O:30])[C:24]#[N:25].C(=O)(O)[O-].[Na+]>C([O-])([O-])=O.[Na+].[Na+]>[C:11]([O:10][C:8]([NH:7][C@@H:3]([C@@H:2]([NH:1][C:21]1[CH:22]=[C:23]([C:24]#[N:25])[CH:26]=[CH:27][C:28]=1[N+:29]([O-:31])=[O:30])[CH3:15])[C:4]([OH:6])=[O:5])=[O:9])([CH3:14])([CH3:13])[CH3:12]

Participants

Conditions

Temperature: 55 °C

Procedure

A mixture of (2S,3S)-3-amino-2-(tert-butoxycarbonylamino)butanoic acid (3.14 g, 14.4 mmol), dimethylsulfoxide (40 ml), 3-fluoro-4-nitrobenzonitrile (2.63 g, 15.8 mmol), and sodium bicarbonate (4.83 g, 57.5 mmol) was stirred at 55° C. for 3 h. Additional NaHCO3 (0.9 g) was added and the mixture was stirred at 60° C. for 1 hour, then cooled to RT, diluted with cold sat. Na2CO3, and washed with MTBE. The aqueous phase was carefully acidified to pH ˜4 with solid citric acid and extracted with EtOAc (three times). The combined organic layers were washed with H2O twice and brine, dried over Na2SO4, filtered, and concentrated to provide (2S,3S)-2-(tert-butoxycarbonylamino)-3-(5-cyano-2-nitrophenylamino)butanoic acid (5.7 g, quant.).

Workup

stirringthe mixture was stirred at 60° C. for 1 hour
temperaturecooled to RT
washwashed with MTBE
extractionextracted with EtOAc (three times)
washThe combined organic layers were washed with H2O twice
dry with materialbrine, dried over Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-ce5bd089586e46c1aaff2df77e857bee
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422331B2

Reaction notes

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