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  (Organic Chemistry)

Nitrile to Amide

(Basic Conditions)


Example 1

The SM (120 mg, 0.35 mmol) was suspended in MeOH (0.5 mL) and H2O (O.5 mL) and stirred at RT. To this mixture was added 50% aq NaOH (84 mg, 1.05 mmol). Upon warming to 50 C a small amount of dioxane was added to aid in solubility. After 90 min the mixture was removed from heat and H2O was added to precipitate a solid. The solid was filtered and washed with H2O to provide the product. [87 mg]

[Patent Reference: WO2010038081, page 250, (33.8 MB)]

Example 2

A mixture of the SM (500 mg, 3.65 mmol) and KOH (1.02 g, 18.2 mmol) in 80% EtOH  (10 mL) was heated at reflux for 16 h. The reaction mixture was cooled to RT and concentrated in vacuo. The residue was diluted with H2O, acidified with AcOH, and extracted with EtOAc. The combined organics were dried (MgSO4) and concentrated. The resulting material was purified by flash chromatography (eluting with 20-60% EtOAc/heptane) to provide the product as a white solid. [210 mg]

[Patent Reference: WO2012069948, page 63, (3.9 MB)]

Example 3

To a solution of the SM (0.12 g, 0.29 mmol) in 2:2:1 THF/MeOH/H2O (5 mL) at 0 C was added dropwise 4M aq LiOH (0.44 mL, 1.76 mmol). The mixture was allowed to warm to RT while stirring continued for 4 h. The mixture was acidified with 1M HCl (6 mL) and extracted with EtOAc (3 x 10 mL). The combined organics were washed with H2O (10 mL), brine (10 mL), dried (Na2SO4), and concentrated to provide the product as a yellow solid. [60 mg, 47%]

[Patent Reference: WO2015129926, page 83, (21.5 MB)]

Example 4

A mixture of the SM (65 mg, 0.21 mmol) and NaOH (17 mg, 0.42 mmol) in 1:1 EtOH/H2O (2 mL) was stirred at 50 C for 4 h. After cooling to RT, the mixture was adjusted to pH = 7 using 3N HCl. The mixture was concentrated and purified by Prep HPLC [5-95%, (ACN)/(0.5% TFA in H2O)] to provide the product as a white solid. [27 mg, 39%]

[Patent Reference: WO2016011390, page 79, (20.2 MB)]