Phosphorus pentachloride → 1-[2-Chloro-3-(1-methylcyclohexyl)methoxypropyl]pyrrolidine

HRID 477448Notes

Reaction equation

HRID 477448 reaction equation
P(Cl)(Cl)(Cl)(Cl)[Cl:2].[CH3:7][C:8]1([CH2:14][O:15][CH2:16][CH:17](O)[CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1>C1(C)C=CC=CC=1>[Cl:2][CH:17]([CH2:16][O:15][CH2:14][C:8]1([CH3:7])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]1)[CH2:18][N:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

4

Reactant 2

HCID 24819Phosphorus pentachlorideHCID 14097063alpha-[((1-Methylcyclohexyl)methoxy)methyl]-1-pyrrolidineethanol

Product 1

HCID 140970641-[2-Chloro-3-(1-methylcyclohexyl)methoxypropyl]pyrrolidineYield 70.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
10 °C

Procedure

A 500 ml three necked round bottom flask was equipped with a mechanical stirrer, addition funnel, thermometer and an argon inlet and outlet. PCl5 (33 g; 0.159 mole) and 8 ml of dry toluene was added to the reaction vessel. 8.5 g (0.151 mole) of alpha-[((1-methylcyclohexyl)methoxy)methyl]-1-pyrrolidineethanol (the compound of Example 7b) was added to the addition funnel along with 5 ml of toluene. Hydrogen chloride gas was bubbled into the addition funnel until the solution was acidic. The PCl5 suspension was cooled to 10° C. and the amino alcohol hydrochloride solution was added dropwise, maintaining the temperature between 10°-15° C. After the addition was complete, the ice bath was removed and the mixture stirred at RT for 1.5 hr. A two liter beaker containing 116 ml of 45% potassium hydroxide and 210 g of ice was cooled in an ice bath. The reaction mixture (a clear yellow solution) was transferred to a separatory funnel and added portionwise at a rate to keep the reaction temperature at 25°-35° C. Stirring was continued for 0.5 hr after the addition. The reaction was transferred to a two liter separatory funnel and diluted with water and ether. The water layer was extracted twice with ether and the combined ether extracts were washed twice with water, once with brine, dried over anhydrous potassium carbonate and concentrated in vacuo to give 29.12 g of the title compound.

Workup

  1. customHydrogen chloride gas was bubbled into the addition funnel until the solution
  2. additionthe amino alcohol hydrochloride solution was added dropwise
  3. temperaturemaintaining the temperature between 10°-15° C
  4. additionAfter the addition
  5. customthe ice bath was removed
  6. additionA two liter beaker containing 116 ml of 45% potassium hydroxide and 210 g of ice
  7. temperaturewas cooled in an ice bath
  8. customThe reaction mixture (a clear yellow solution) was transferred to a separatory funnel
  9. additionadded portionwise at a rate
  10. customat 25°-35° C
  11. stirringStirring
  12. waitwas continued for 0.5 hr
  13. additionafter the addition
  14. customThe reaction was transferred to a two liter separatory funnel
  15. additiondiluted with water and ether
  16. extractionThe water layer was extracted twice with ether
  17. washthe combined ether extracts were washed twice with water, once with brine
  18. dry with materialdried over anhydrous potassium carbonate
  19. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-23001e86b5e74189ade2c332a0628ff6
Source dataset
uspto-grants-1989_12
Patent number
US04888335

Reaction notes

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