Triethylamine → tert-Butyl 2-chloro-6-vinylisonicotinate

HRID 1909133Notes

Reaction equation

HRID 1909133 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([Cl:15])[N:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[CH:16]([B-](F)(F)F)=[CH2:17].[K+].C(N(CC)CC)C.C(=O)(O)[O-].[Na+]>C1COCC1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Cl:15][C:13]1[CH:12]=[C:4]([CH:3]=[C:2]([CH:16]=[CH2:17])[N:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 22594123tert-Butyl 2,6-dichloropyridine-4-carboxylateHCID 23679353Potassium vinyltrifluoroborate

Product 1

HCID 86657031tert-Butyl 2-chloro-6-vinylisonicotinate

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of tert-butyl 2,6-dichloroisonicotinate (11.0 g, 44.3 mmol) in THF (200 mL) were added potassium vinyltrifluoroborate (7.1 g, 53.2 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.97 g, 1.33 mmol) and triethylamine (9.3 mL, 66.5 mmol). The mixture was heated to 65° C. After 1 h, saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate (3×). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by silica gel chromatography (100% hexanes→90% hexanes/ethyl acetate) gave no separation of desired product. The mixture was carried onto next step.

Workup

  1. extractionthe mixture was extracted with ethyl acetate (3×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (100% hexanes→90% hexanes/ethyl acetate)
  7. customgave
  8. customno separation of desired product

Sources & evidence

ORD record
ord-b1ef76f1dd724efba1104e1d847d998f
Source dataset
uspto-grants-2013_12
Patent number
US08598209B2

Reaction notes

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