1-Bromopropane → HCID 13671256, compound

HRID 2106889Notes

Reaction equation

HRID 2106889 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH:14]=2)[CH:6]=[CH:7][CH:8]=1.[CH2:16]([Li])[CH2:17][CH2:18]C.C(Br)CC>C1COCC1.CCCCCC>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2([CH2:16][CH2:17][CH3:18])[CH:10]=[CH:11][N:12]([CH3:15])[CH2:13][CH2:14]2)[CH:6]=[CH:7][CH:8]=1

Participants

6

Reactant 3

HCID 78401-BromopropaneHCID 1557781-Methyl-4-(3-methoxyphenyl)-1,2,3,6-tetrahydropyridineHCID 178418339Butyllithium

Product 1

HCID 13671256HCID 13671256, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-5 °C

Procedure

A solution of 900 g (4.43 mol) of 1,2,3,6-tetrahydro-4-(3-methoxyphenyl)-1-methylpyridine dissolved in 10.8 liters of dry THF was added to a dry, nitrogen purged 22 liter reaction flask equipped with a stirrer, low temperature thermometer, and addition funnel. The temperature of the reaction mixture was lowered to approximately -10° C. whereupon 3.04 liters of 1.6 molar n-butyllithium in hexane was added at a rate so as to maintain the temperature below -5° C. The resulting deep red solution was stirred for 15 minutes at -5° C. and 572 g (4.65 mol) of n-propylbromide in 2.4 liters of dry tetrahydrofuran were added at such a rate so that the temperature remained below -5° C. The reaction mixture was stirred for 10 minutes at -5° C. and then carefully quenched by the addition of 1.5 liters of water to destroy any excess n-butyllithium. The organic phase was separated, washed with 1.5 liters of water, 1.5 liters of saturated sodium chloride solution and dried over 500 g of anhydrous sodium sulfate. Evaporation of the solvent gave 1126 g of crude 1,2,3,4-tetrahydro-4-(3-methoxyphenyl)-1-methyl-4-propylpyridine (75% pure). 78% yield. bp=113° C./0.2 torr. NMR: (CDCl3) δ0.80 (3H,t), 2.57 (3H,s), 3.80 (3H,s), 4.58 (1H,d,A of AX, J =8), 5.95 (1H,d,X of AX, J=8), 6.8-7.3 (4H, m, aryl).

Workup

  1. additionwas added to a dry, nitrogen
  2. custompurged
  3. custom22 liter reaction flask
  4. customequipped with a stirrer
  5. additionlow temperature thermometer, and addition funnel
  6. additionwas added at a rate so as
  7. temperatureto maintain the temperature below -5° C
  8. customremained below -5° C
  9. stirringThe reaction mixture was stirred for 10 minutes at -5° C.
  10. customcarefully quenched by the addition of 1.5 liters of water
  11. customto destroy any excess n-butyllithium
  12. customThe organic phase was separated
  13. washwashed with 1.5 liters of water, 1.5 liters of saturated sodium chloride solution
  14. dry with materialdried over 500 g of anhydrous sodium sulfate
  15. customEvaporation of the solvent

Sources & evidence

ORD record
ord-efbb573225b24e75b896198563287e23
Source dataset
uspto-grants-1990_06
Patent number
US04931558

Reaction notes

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