Nitrogen → 2-Pyridinecarboxylic acid, 3-chloro-5-cyano-, 1,1-dimethylethyl ester
Reaction equation
Br[C:2]1[CH:3]=[C:4]([Cl:15])[C:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[N:6][CH:7]=1.[C:16]([Zn]C#N)#[N:17].N#N.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>CN(C=O)C.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:15][C:4]1[C:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[N:6][CH:7]=[C:2]([C:16]#[N:17])[CH:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 95 °C
Procedure
A mixture of tert-butyl 5-bromo-3-chloropicolinate (12 g, 41.0 mmol), dicyanozinc (3.37 g, 28.7 mmol), and zinc (0.375 g, 5.74 mmol) were suspended in DMF (82 ml) in round bottom flak. The suspension was purged with N2 and finally Pd2(dba)3 (1.878 g, 2.051 mmol), tri-tert-butylphosphine (6.2 ml, 6.15 mmol) and neat tri-tert-butylphosphine (300 mg), was added under the Ar. The r×n mixture was heated to 95° C. for 3 h. Then another 2.8 g of Pd2(dba)3 and 1.2 g of neat P ligand were added. 3.5 h later, it was cooled to RT and black precipitate was filtered out by filtration. The filtrate was diluted with 150 ml of MTBE. The organic layer was washed with 100 ml of water and brine. It was dried on MgSO4 and concentrated which was carried over to next step directly. MS m/z=261.0/263.0 (M+Na).
Workup
- additionwas added under the Ar
- temperature3.5 h later, it was cooled to RT
- filtrationblack precipitate was filtered out by filtration
- additionThe filtrate was diluted with 150 ml of MTBE
- washThe organic layer was washed with 100 ml of water and brine
- customIt was dried on MgSO4
- concentrationconcentrated which
Sources & evidence
- ORD record
- ord-284939929b5746f68d90bb24f8fc1ce9
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09309263B2
Reaction notes
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