Potassium Carbonate → (R)-2-(4-cyano-3-(trifluoromethyl)phenylamino)-3,3-dimethylbutanoic acid

HRID 238560Notes

Reaction equation

F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1.[NH2:14][C@H:15]([C:19](O)([CH3:21])[CH3:20])[C:16]([OH:18])=[O:17].[C:23]([O-])([O-])=O.[K+].[K+]>CS(C)=O>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([NH:14][C@H:15]([C:19]([CH3:21])([CH3:23])[CH3:20])[C:16]([OH:18])=[O:17])=[CH:3][C:4]=1[C:10]([F:13])([F:12])[F:11])#[N:7]

Participants

Conditions

Temperature: 85 °C

Procedure

4-fluoro-2-(trifluoromethyl)benzonitrile (7.10 g, 37.55 mmol) was mixed together with (R)-2-amino-3-hydroxy-3-methylbutanoic acid (5 g, 37.55 mmol) in DMSO (220 mL). K2CO3 (15.57 g, 112.65 mmol) was added to the reaction mixture and the reaction mixture stirred at 85° C. for 96 h. The reaction mixture was allowed to cool to room temperature and quenched with H2O (40 mL) and extracted with EtOAc (2×80 mL). The aqueous layer was then acidified with solid citric acid and extracted with EtOAc (2×80 mL). The later organic extracts were combined, washed with H2O (2×30 mL), dried (Na2SO4), filtered and concentrated under reduced pressure to provided the title compound as a pale yellow solid (11.1 g, 98%): 1H NMR (400 MHz, d6-acetone, δ in ppm) 7.57 (d, J=9 Hz, 1H), 6.98 (d, J=2 Hz, 1H), 6.80 (dd, J=9 and 2 Hz, 1H), 5.52 (br s, 1H), 3.96 (d, J=7 Hz, 1H), 1.42 (s, 3H), and 1.36 (s, 3H).

Workup

temperatureto cool to room temperature
customquenched with H2O (40 mL)
extractionextracted with EtOAc (2×80 mL)
extractionextracted with EtOAc (2×80 mL)
washwashed with H2O (2×30 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-e7fe0bed3783497889442ff4bed9d9d6
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08642632B2

Reaction notes

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