Dichloromethane → 4-[5-(1-methyl-1H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

HRID 1020955Notes

Reaction equation

HRID 1020955 reaction equation
Br[C:2]1[S:6][C:5]([C:7]2[N:11]=[CH:10][N:9]([CH3:12])[N:8]=2)=[CH:4][CH:3]=1.[C:13]([O:17][C:18]([N:20]1[CH2:25][CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14].ClCCl.C([O-])([O-])=O.[Na+].[Na+].[O-]S([O-])(=O)=O.[Mg+2]>O1CCOCC1>[C:13]([O:17][C:18]([N:20]1[CH2:21][CH:22]=[C:23]([C:2]2[S:6][C:5]([C:7]3[N:11]=[CH:10][N:9]([CH3:12])[N:8]=3)=[CH:4][CH:3]=2)[CH2:24][CH2:25]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 24083Sulfuric acid magnesium salt (1:1)HCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 583719633-(5-bromo-thiophen-2-yl)-1-methyl-1H-[1,2,4]triazole

Product 1

HCID 583719164-[5-(1-methyl-1H-[1,2,4]triazol-3-yl)-thiophen-2-yl]-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl esterYield 86.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a large pressure flask were charged compound 3-(5-bromo-thiophen-2-yl)-1-methyl-1H-[1,2,4]triazole (3.1 g, 12.8 mmols) (5BW), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (3.6 g, 11.65 mmols), [1,1′-bis(diphenylphosphino)-ferrocene]dichloro-palladium (II), complex with dichloromethane (1:1) (0.475 g, 0.89 mmols), Na2CO3 (8.5 ml) and dioxane (40 ml). The mixture was briefly degassed with Ar for ˜0.5 minute, capped and stirred at 80° C. overnight. After cooling, the reaction mixture was diluted with EtOAc and brine. Organic layer was isolated, and dried MgSO4. After concentration, the residue was purified on silica gel. Elution with EtOAc (100%) gave the desired product (6BW) (3.5 g).

Workup

  1. customThe mixture was briefly degassed with Ar for ˜0.5 minute
  2. customcapped
  3. temperatureAfter cooling
  4. additionthe reaction mixture was diluted with EtOAc and brine
  5. customOrganic layer was isolated
  6. concentrationAfter concentration
  7. customthe residue was purified on silica gel
  8. washElution with EtOAc (100%)

Sources & evidence

ORD record
ord-d07ee0f111ea4bc68c79d98e4a57c1f4
Source dataset
uspto-grants-2014_05
Patent number
US08716483B2

Reaction notes

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