N-methyl-2-pyrrolidone → HCID 68511164, compound

HRID 1426322Notes

Reaction equation

Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]([OH:14])=[O:13])[CH:3]=1.[CH3:15][N:16]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:15]([C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([C:12]([OH:14])=[O:13])[CH:3]=1)#[N:16]

Participants

Conditions

Temperature: 160 °C

Procedure

4-Bromo-6-(trifluoromethyl)pyridine-2-carboxylic acid (0.150 g, 0.556 mmol, Anichem) and zinc cyanide (0.39 g, 3.3 mmol) were mixed in N-methylpyrrolidinone (2 mL) and the mixture was degassed by bubbling a stream of nitrogen through the mixture for 10 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.096 g, 0.083 mmol) was added, the degassing was continued for 5 minutes, then the reaction was sealed and heated in the microwave to a temperature of 160° C. for 15 minutes. The mixture was filtered and purified by preparative HPLC (eluting with a gradient from 18.8 to 40.9% MeCN/H2O containing 0.1% TFA over 1-6 min at 60 mL/min thru C18 SunFire 30×100 mm, 5 um particle size) using UV detection. The product eluted at 5.25 minutes.

Workup

customthe mixture was degassed
customby bubbling a stream of nitrogen through the mixture for 10 minutes
customthe reaction was sealed
filtrationThe mixture was filtered
custompurified by preparative HPLC (
washeluting with a gradient from 18.8 to 40.9% MeCN/H2O containing 0.1% TFA over 1-6 min at 60 mL/min
washThe product eluted at 5.25 minutes

Sources & evidence

ORD record: ord-fc852153200f4607bf7cbaf5913e0a30
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08933085B2

Reaction notes

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