2-Chloro-4-fluorobenzonitrile → HCID 59516164, compound

HRID 1160389Notes

Reaction equation

HRID 1160389 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8](F)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[NH2:11][C@@H:12]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:13]([OH:15])=[O:14].C([O-])(O)=O.[Na+]>CS(C)=O.O>[Cl:1][C:2]1[CH:9]=[C:8]([NH:11][C@@H:12]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:13]([OH:15])=[O:14])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

6

Reactant 3

HCID 1090002-Chloro-4-fluorobenzonitrileHCID 516892Sodium BicarbonateHCID 70105704-tert-Butyl hydrogen L-aspartate

Product 1

HCID 59516164HCID 59516164, compoundYield 80.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×

Procedure

2-Chloro-4-fluorobenzonitrile (2.13 g, 13.8 mmol), (2S)-2-amino-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoic acid (2.6 g, 13.8 mmol) and NaHCO3 (3.5 g, 41.4 mmol) in DMSO (70 mL) and H2O (10 mL) were stirred at 95° C. for 15 h. After cooling, the reaction mixture was diluted with H2O (100 mL) and washed with Et2O (100 mL). The H2O layer was acidified to Congo Red midpoint and extracted with Et2O (2×). The combined organic extracts were washed with H2O, dried over Na2SO4, filtered, and concentrated to give the titled product (3.59 g, 80%) as a foam. 1H-NMR (CDCl3) δ: 1.45 (9H, s), 2.89 (2H, m), 3.54 (1H, m), 4.42 (1H, m), 6.55 (1H, d, J=8.8 Hz), 6.70 (1H, s), 7.43 (1H, d, J=8.4 Hz). LC-MS (ES) m/e 325.4 (M+H)+.

Workup

  1. temperatureAfter cooling
  2. washwashed with Et2O (100 mL)
  3. extractionextracted with Et2O (2×)
  4. washThe combined organic extracts were washed with H2O
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c27368e9aa0d450b899c47fa43380268
Source dataset
uspto-grants-2010_10
Patent number
US07816395B2

Reaction notes

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