Tetrahydrofuran → tert-Butyl 4-(3-isopropylphenyl)-3,6-dihydropyridine-1(2H)-carboxylate

HRID 61424Notes

Reaction equation

HRID 61424 reaction equation
FC(F)(F)S(O[C:7]1[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH:12]=1)(=O)=O.[CH:22]([C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][CH:30]=1)([CH3:24])[CH3:23].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCCC1>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>[CH:22]([C:25]1[CH:30]=[C:29]([C:7]2[CH2:8][CH2:9][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:11][CH:12]=2)[CH:28]=[CH:27][CH:26]=1)([CH3:24])[CH3:23]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 27734783-Isopropylbenzeneboronic acidHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate

Product 1

HCID 86598246tert-Butyl 4-(3-isopropylphenyl)-3,6-dihydropyridine-1(2H)-carboxylate

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

A mixture of tert-butyl 4-[(trifluoromethyl)sulfonyl]oxy-3,6-dihydropyridine-1(2H)-carboxylate (11.0 g, 0.0332 mol), (3-isopropylphenyl)boronic acid (5.44 g, 0.0332 mol) and potassium phosphate (21.1 g, 0.0996 mol) in tetrahydrofuran (150.0 mL, 1.849 mol) was degassed for 15 min, then tetrakis(triphenylphosphine)palladium(0) (2 g, 0.002 mol) was added and the resulting mixture was refluxed overnight. After evaporation of most of THF, the residue was diluted with water, extracted with EtOAc. The combined organic layers were washed with brine, dried and evaporated to dry. The residue was applied on silica gel column, eluting with 0 to 20% EtOAc in hexane (9.1 g, 91%). MS (ESI): (M-Bu) 246.1.

Workup

  1. customwas degassed for 15 min
  2. temperaturethe resulting mixture was refluxed overnight
  3. customAfter evaporation of most of THF
  4. additionthe residue was diluted with water
  5. extractionextracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. customdried
  8. customevaporated
  9. customto dry
  10. washeluting with 0 to 20% EtOAc in hexane (9.1 g, 91%)

Sources & evidence

ORD record
ord-8f0e175c68b24649bcf0bd7f477f23f7
Source dataset
uspto-grants-2016_09
Patent number
US09440958B2

Reaction notes

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