Dimethylformamide → 4-[4-chloro-2-(3-chloro-benzoylamino)-phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid

HRID 1810975Notes

Reaction equation

HRID 1810975 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[NH:9][C:10](=[O:18])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=1.C([O:23][C:24]([N:26]1[CH2:31][CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH2:28][CH2:27]1)=[O:25])(C)(C)C.C([O-])([O-])=O.[Na+].[Na+].CN(C=O)C>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([C:29]2[CH2:30][CH2:31][N:26]([C:24]([OH:25])=[O:23])[CH2:27][CH:28]=2)=[C:3]([NH:9][C:10](=[O:18])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)[CH:4]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 59548898N-(2-bromo-5-chloro-phenyl)-3-chloro-benzamide

Product 1

HCID 866469174-[4-chloro-2-(3-chloro-benzoylamino)-phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acidYield 88.8%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

In a 20 mL microwave tube is added N-(2-bromo-5-chloro-phenyl)-3-chloro-benzamide (0.500 g, 1.45 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.532 g, 1.74 mmol), bis(triphenylphosphine) palladium(II) chloride (0.102 g, 0.145 mmol), 2N Na2CO3 aqueous solution (3.62 mL, 7.25 mmol) and DMF (10 mL). The resulting mixture is placed in a microwave oven and heated to 100° C. for 30 min. The reaction turns black. The reaction mixture is poured into water (30 mL) and filtered. The cake is washed with 10 mL water and air dried. The cake is then dissolved in minimum dichloromethane and purified via flash chromatography using 0-30% EtOAc/hexane. The compound comes at 30% EtOAc. Removal of the solvent under vacuum gives 0.504 g of 4-[4-chloro-2-(3-chloro-benzoylamino)-phenyl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tent-butyl ester in 78% yield.

Workup

  1. customThe resulting mixture is placed in a microwave oven
  2. filtrationfiltered
  3. washThe cake is washed with 10 mL water and air
  4. customdried
  5. dissolutionThe cake is then dissolved in minimum dichloromethane
  6. custompurified via flash chromatography
  7. customRemoval of the solvent under vacuum

Sources & evidence

ORD record
ord-b82705cbf4934142b73566fd53d3841b
Source dataset
uspto-grants-2013_01
Patent number
US08362249B2

Reaction notes

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