Sodium Carbonate → HCID 67155395, compound

HRID 1897668Notes

Reaction equation

HRID 1897668 reaction equation
Br[C:2]1[C:8]([Cl:9])=[CH:7][C:5]([NH2:6])=[C:4]([CH3:10])[CH:3]=1.CC1(C)C(C)(C)OB([C:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O.[Pd].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.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>[NH2:6][C:5]1[C:4]([CH3:10])=[CH:3][C:2]([C:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH:20]=2)=[C:8]([Cl:9])[CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 71720264-bromo-5-chloro-2-methylaniline

Product 1

HCID 67155395HCID 67155395, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 4-bromo-5-chloro-2-methylaniline (500 mg, 2.27 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5,6-dihydropyridine-1(2H)-carboxylate (840 mg, 3.73 mmol) and sodium carbonate (2.52 g, 15.9 mmol) in DMF/H2O (20/5 mL) was added tetrakis(triphenylphosphine) palladium (0) (131 mg, 5 mol %). The reaction tube was sealed, the mixture was purged with N2 for 3 min and then heated at 100° C. under N2 for overnight. The reaction was cooled to room temperature and poured into saturated aqueous ammonia chloride solution. The crude reaction mixture was extracted with ethyl acetate (3×15 mL). The organic extracts were combined, washed with brine and concentrated. The crude product was purified with silica chromatography (80% ethyl acetate in hexanes) to afford tert-butyl 4-(4-amino-2-chloro-5-methylphenyl)-5,6-dihydropyridine-1(2H)-carboxylate as a yellow solid. This obtained product (322 mg, 1 mmol) was dissolved in dioxane/NMP (anhydrous, 4 mL, 3/1). To this solution was added tributyl(vinyl)stannane (380 mg, 1.2 mmol), cesium fluoride (304 mg, 2 mmol) and palladium bis(tri-tert-butyl-phosphine) (51 mg, 10 mol %). This mixture was purged with N2 for 3 minutes and then heated in a sealed tube at 120° C. for overnight. The mixture was cooled to room temperature and diluted with ethyl acetate. The resulting mixture was sequentially washed with saturated aqueous ammonium chloride and brine, and finally dried over sodium sulfate. After concentration, the crude product was purified via silica chromatography (10% ethyl acetate in hexanes) to afford tert-butyl 4-(4-amino-5-methyl-2-vinylphenyl)-5,6-dihydropyridine-1(2H)-carboxylate as a light yellow oil; ESMS m/z 215.2 (M−Boc+H+).

Workup

  1. customThe reaction tube was sealed
  2. customthe mixture was purged with N2 for 3 min
  3. temperatureThe reaction was cooled to room temperature
  4. additionpoured into saturated aqueous ammonia chloride solution
  5. customThe crude reaction mixture
  6. extractionwas extracted with ethyl acetate (3×15 mL)
  7. washwashed with brine
  8. concentrationconcentrated
  9. customThe crude product was purified with silica chromatography (80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-e741578f2045493fba31a2cd8ed25b66
Source dataset
uspto-grants-2013_08
Patent number
US08519129B2

Reaction notes

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