Triphenylphosphine → HCID 68767182, compound

HRID 2065888Notes

Reaction equation

HRID 2065888 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8](Cl)=[N:7][CH:6]=1)[CH3:2].C1C=CC(P([C:27]2[CH:32]=[CH:31]C=CC=2)C2C=CC=CC=2)=CC=1.O1CCOC[CH2:34]1>C([O-])([O-])=O.[K+].[K+].CCOCC.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>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([CH:34]=[C:32]([CH3:31])[CH3:27])=[N:7][CH:6]=1)[CH3:2]

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 16762519Ethyl 5,6-Dichloronicotinate

Product 1

HCID 68767182HCID 68767182, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5,6-dichloronicotinic acid ethyl ester (2.40 g, 10.9 mmol) and 2,4,6-tris-(2-methyl-propenyl)-cyclotriboroxane pyridine complex (2.02 g, 6.22 mmol, prepared in analogy to a procedure given by F. Kerins, D. F. O'Shea J. Org. Chem. 67 (2002) 4968-4971) in dioxane (40 mL) and 2 M aq. K2CO3 solution (10 mL), PPh3 (114 mg, 0.436 mmol) is added. The mixture is degassed and put under N2 before Pd(PPh3)4 (160 mg, 0.218 mmol) is added. The mixture is stirred at 100° C. for 1.5 h before another portion of 2,4,6-tris-(2-methyl-propenyl)-cyclotriboroxane pyridine complex (1.01 g, 3.11 mmol) is added. Stirring is continued at 100° C. for 3 h before the mixture is cooled to rt, diluted with ether, washed with 1N aq. NaOH solution followed by water, dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 5-chloro-6-(2-methyl-propenyl)-nicotinic acid ethyl ester (2.4 g) as an oil; LC-MS: tR=1.05 min, [M+1]+=240.02. To a solution of this material in dioxane (40 mL), 2,4,6-trivinylcyclotriboroxane pyridine complex (1.84 g, 7.63 mmol), Cs2CO3 (4.62 g, 14.2 mmol) followed by tri-tert-butylphosphine (88 mg, 0.436 mmol) is added. The mixture is degassed and put under N2 before Pd2(dba)3 (200 mg, 0.218 mmol) is added. The mixture is stirred at 100° C. for 16 h before another portion of 2,4,6-trivinylcyclotriboroxane pyridine complex (1.84 g, 7.63 mmol) and Pd2(dba)3 (200 mg, 0.218 mmol) is added. Stirring is continued at 100° C. for 24 h before the mixture is diluted with EA, washed with 1N aq. NaOH solution, dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 10:1 to give a first portion of 6-(2-methyl-propenyl)-5-vinyl-nicotinic acid ethyl ester. In addition, unreacted 5-chloro-6-(2-methyl-propenyl)-nicotinic acid ethyl ester is isolated. This material is again treated with 2,4,6-trivinylcyclotriboroxane pyridine complex as described before. Work-up, purification and combining the two portions give 6-(2-methyl-propenyl)-5-vinyl-nicotinic acid ethyl ester (1.37 g) as an oil; LC-MS: tR=0.87 min, [M+1]+=232.13.

Workup

  1. customThe mixture is degassed
  2. additionis added
  3. additionis added
  4. stirringStirring
  5. waitis continued at 100° C. for 3 h before the mixture
  6. temperatureis cooled to rt
  7. washwashed with 1N aq. NaOH solution
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product is purified by CC on silica gel eluting with heptane:EA 9:1

Sources & evidence

ORD record
ord-1c90242f17ca46ba91d1fdd2e40998b0
Source dataset
uspto-grants-2012_10
Patent number
US08288554B2

Reaction notes

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