Hydrochloric Acid → HCID 20475372, compound

HRID 2295391Notes

Reaction equation

HRID 2295391 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:3]=1.CC1C(C2C=CC=CN=2)=NC(C)=CC=1.CC1C(C2C=CC=CN=2)=NC=C(C)C=1.C([N-]C(C)C)(C)C.[Li+].O1CCCC1.CCCCCC.C(NC(C)C)(C)C.Cl[CH2:70][O:71][CH2:72][C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1.Cl>O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C>[CH2:72]([O:71][CH2:70][CH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:3]=1)[C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1

Participants

11

Reactant 8

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 137983Benzyl chloromethyl etherHCID 2724682Lithium diisopropylamideHCID 11008603HCID 11008603, compoundHCID 12232398HCID 12232398, compoundHCID 12232399HCID 12232399, compoundHCID 21883165Tetrahydrofuran hexane

Product 1

HCID 20475372HCID 20475372, compoundYield 78%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolvent2×

Conditions

Temperature
23 °C

Procedure

36.4 g (0.2 mol) of a mixture of isomers, consisting of 4,6-dimethyl-2,2'-bipyridine (45% by weight), 3,6-dimethyl-2,2'-bipyridine (45% by weight) and 3,5-dimethyl-2,2'-bipyridine (10% by weight) are dissolved in 150 ml of anhydrous tetrahydrofuran (THF). At 0° C., a solution of lithium diisopropylamide and hexamethylphosphoric acid triamide in THF/n-hexane [ratio about 1:1 by volume; prepared from 12.2 g (0.12 mol) of diisopropylamine in 50 ml of anhydrous THF, 60 ml of 2-molar n-butyllithium solution in n-hexane and 25.9 g (0.12 mol) of anhydrous hexamethylphosphoric acid triamide] is added dropwise in the course of 2 hours. Subsequently, the mixture is stirred for 30 minutes at 0° C. and for 15 minutes at 23° C. At -75° C., 20.3 g (0.13 mol) of benzyl chloromethyl ether are added dropwise in the course of 30 minutes. The reaction mixture is warmed slowly to 23° C., stirred for 1 hour at this temperature and then added to 200 ml of 10% hydrochloric acid. The solution is washed with three times 250 ml of ethyl acetate. The aqueous phase is rendered alkaline with potassium carbonate and the product obtained is extracted with four times 250 ml of ethyl acetate. The combined ethyl acetate phases are dried over sodium sulfate and the solvent is removed in vacuo. The residue is distilled in a high vacuum. The initial fraction (16.8 g; boiling point 75°-83° C./0.27 Pa) contains 78% by weight of 3,6-dimethyl-2,2'-bipyridine, 14% by weight of 3,5-dimethyl-2,2'-bipyridine and 3% by weight of unconverted 4,6-dimethyl-2,2'-bipyridine. At 174°-176° C./0.09 Pa, 20.3 g of 4-[2-(benzyloxy)-ethyl]-6-methyl-2,2'-bipyridine distil over; yield 78% of theory, calculated on the 4,6-dimethyl-2,2'-bipyridine present in the mixture of isomers employed. nD20 =1.6007.

Workup

  1. temperatureThe reaction mixture is warmed slowly to 23° C.
  2. stirringstirred for 1 hour at this temperature
  3. washThe solution is washed with three times 250 ml of ethyl acetate
  4. customthe product obtained
  5. extractionis extracted with four times 250 ml of ethyl acetate
  6. dry with materialThe combined ethyl acetate phases are dried over sodium sulfate
  7. customthe solvent is removed in vacuo
  8. distillationThe residue is distilled in a high vacuum
  9. customAt 174°-176° C./0.09 Pa, 20.3 g of 4-[2-(benzyloxy)-ethyl]-6-methyl-2,2'-bipyridine distil over
  10. additionyield 78% of theory, calculated on the 4,6-dimethyl-2,2'-bipyridine present in the mixture of isomers

Sources & evidence

ORD record
ord-9507f99c60d542dda169b902036ce837
Source dataset
uspto-grants-1984_01
Patent number
US04424359

Reaction notes

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