Potassium Phosphate, Tribasic → Tert-Butyl 4-[4-Chloro-2-(2-Methoxy-2-Oxoethyl)Phenyl]-3,6-Dihydropyridine-1(2H)-Carboxylate

HRID 2415540Notes

Reaction equation

HRID 2415540 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:13][CH:14]=2)O1.[CH3:23][O:24][C:25](=[O:35])[CH2:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1Br.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C)C=O.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>[Cl:33][C:31]1[CH:30]=[CH:29][C:28]([C:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:16])[CH2:13][CH:14]=2)=[C:27]([CH2:26][C:25]([O:24][CH3:23])=[O:35])[CH:32]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 22640779Methyl 2-(2-bromo-5-chlorophenyl)acetate

Product 1

HCID 22640774Tert-Butyl 4-[4-Chloro-2-(2-Methoxy-2-Oxoethyl)Phenyl]-3,6-Dihydropyridine-1(2H)-CarboxylateYield 58.3%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A vigorously stirred mixture of the tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,6-dihydropyridine-1(2H)-carboxylate (1-4) (1.40 g, 4.53 mmol), methyl(2-bromo-5-chlorophenyl)acetate (1-2) (1.31 g, 4.98 mmol), potassium phosphate tribasic (2.85 g, 13.6 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.262 g, 0.227 mmol) in N,N-dimethylformamide (22 mL) was degassed via three vacuum/nitrogen ingress cycles and then heated at 100° C. for approximately 18 h. After cooling to room temperature, the reaction mixture was poured into water and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel (gradient elution; 0%-25% ethyl acetate/hexanes as eluent) afforded 1-5 (0.967 g) as a colorless oil.

Workup

  1. customwas degassed via three vacuum/nitrogen ingress cycles
  2. temperatureAfter cooling to room temperature
  3. additionthe reaction mixture was poured into water
  4. extractionextracted three times with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customPurification of the crude residue by flash chromatography on silica gel (gradient elution; 0%-25% ethyl acetate/hexanes as eluent)

Sources & evidence

ORD record
ord-5c514bad49a846c9abb888e250e7d281
Source dataset
uspto-grants-2004_11
Patent number
US06818658B2

Reaction notes

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