Potassium Acetate → tert-butyl 5-(3-(4-(methoxycarbonyl)phenoxy)pyrazin-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate

HRID 887483Notes

Reaction equation

HRID 887483 reaction equation
C([O-])(=O)C.[K+].Cl[C:7]1[C:8]([O:13][C:14]2[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=2)=[N:9][CH:10]=[CH:11][N:12]=1.CC1(C)C(C)(C)OB([C:32]2[CH2:33][CH2:34][CH2:35][N:36]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH:37]=2)O1>CC#N>[CH3:21][O:20][C:18]([C:17]1[CH:22]=[CH:23][C:14]([O:13][C:8]2[C:7]([C:34]3[CH2:33][CH2:32][CH2:37][N:36]([C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])[CH:35]=3)=[N:12][CH:11]=[CH:10][N:9]=2)=[CH:15][CH:16]=1)=[O:19]

Participants

5

Reactant 3

HCID 517044Potassium AcetateHCID 45031065Methyl 4-(3-chloropyrazin-2-yloxy)benzoateHCID 59327225tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 59351326tert-butyl 5-(3-(4-(methoxycarbonyl)phenoxy)pyrazin-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of (amphos)2PdCl2 (0.145 g, 0.205 mmol), potassium acetate (1.045 g, 10.65 mmol), methyl 4-(3-chloropyrazin-2-yloxy)benzoate (1.084 g, 4.10 mmol), and tert-butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate (1.900 g, 6.14 mmol) under N2 was added MeCN (7.0 mL) and Ar degassed water (0.70 mL). The reaction mixture was degassed with Ar (10 min) then heated to 80° C. for 20 h. The reaction mixture was diluted with H2O (20 mL) and extracted with EtOAc (2×10 mL). The combined organic extracts were washed with brine (10 mL), dried (MgSO4), and concentrated. Purification by ISCO (120 g SiO2, 10-100% EtOAc/hexanes) gave tert-butyl 5-(3-(4-(methoxycarbonyl)phenoxy)pyrazin-2-yl)-3,4-dihydropyridine-1(2H)-carboxylate as a yellow oil.

Workup

  1. customdegassed water (0.70 mL)
  2. customThe reaction mixture was degassed with Ar (10 min)
  3. additionThe reaction mixture was diluted with H2O (20 mL)
  4. extractionextracted with EtOAc (2×10 mL)
  5. washThe combined organic extracts were washed with brine (10 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customPurification by ISCO (120 g SiO2, 10-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ab0feeccaee14ca68cdcec0bf1c86d1d
Source dataset
uspto-grants-2012_08
Patent number
US08247418B2

Reaction notes

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