Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylate → tert-Butyl 5',6'-dihydro-[2,4'-bipyridine]-1'(2'H)-carboxylate

HRID 1828314Notes

Reaction equation

HRID 1828314 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11](OS(C(F)(F)F)(=O)=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br-].[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[Zn+]>C1COCC1.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>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 178418723HCID 178418723, compound

Product 1

HCID 16094711tert-Butyl 5',6'-dihydro-[2,4'-bipyridine]-1'(2'H)-carboxylateYield 64%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

Next, a pure solution of 4-trifluoromethanesulfonyloxy-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (18 g, 54 mmol) in THF (˜200 mL) was treated with 2-pyridylzinc bromide 0.5 molar solution in THF (from Aldrich, brown color) (124 mL, 62.5 mmol, 1.15 eq.) followed by Pd(PPh3)4 (from Strem Chemicals) (625 mg). The reaction mixture was heated at 60° C. for 90 minutes. The THF was removed by rotary evaporator. Ethyl acetate (300 mL) and 1 N NaOH (200 mL) were added to the residue, and the zinc salts were removed by filtration. The organic layer was separated and washed with brine (300 mL), dried (MgSO4), and concentrated on the rotary evaporator to give brown oil. Purification by flash chromatography using Hexane:Ethyl acetate 6:4 as eluent gave 9.0 g (64% yield) of 3′,6′-dihydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid tert-butyl ester as colorless oil. 1H NMR (300 MHz, DMSO-d6) δ 1.43 (s, 9H), 2.56 (m, 2H), 3.54 (t, 2H), 4.04 (m, 2H), 6.08 (m, 1H), 7.25 (dd, 1H), 7.56 (d, J=9 Hz, 1H), 7.77 (m, 1H), 8.54 (m, 1H); MS (DCI−NH3) m/z 259 (M+H)+, 277 (M+H+18)+.

Workup

  1. customThe THF was removed by rotary evaporator
  2. additionEthyl acetate (300 mL) and 1 N NaOH (200 mL) were added to the residue
  3. customthe zinc salts were removed by filtration
  4. customThe organic layer was separated
  5. washwashed with brine (300 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated on the rotary evaporator
  8. customto give brown oil
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-7314116f52434a15bd30df6948a82dc1
Source dataset
uspto-grants-2006_06
Patent number
US07057042B2

Reaction notes

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