Hydrochloric Acid → (2R,5S)-2,5-Dipropylpyrrolidine

HRID 490804Notes

Reaction equation

HRID 490804 reaction equation
[CH2:1]([N:8]1[C@H:12]([CH2:13][CH2:14][CH3:15])[CH2:11][CH2:10][C@@H:9]1[CH2:16][CH2:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCCC(=O)CCC(=O)CCC.[OH-].[K+].C(N)C1C=CC=CC=1.C([BH3-])#N.[Na+].Cl>C(O)(=O)C.CO>[CH2:16]([C@H:9]1[CH2:10][CH2:11][C@@H:12]([CH2:13][CH2:14][CH3:15])[NH:8]1)[CH2:17][CH3:18].[CH2:1]([N:8]1[CH:12]([CH2:13][CH2:14][CH3:15])[CH2:11][CH2:10][CH:9]1[CH2:16][CH2:17][CH3:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 7504BenzylamineHCID 14797Potassium Hydroxide2×HCID 5003444Sodium cyanoborohydrideHCID 12210000Decane-4,7-dioneHCID 68878282cis-1-Benzyl-2,5-dipropylpyrrolidine

Product 2

HCID 14564783(2R,5S)-2,5-DipropylpyrrolidineHCID 688765851-Benzyl-2,5-dipropylpyrrolidine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
-15 °C

Procedure

The title compound was prepared from cis-1-benzyl-2,5-dipropylpyrrolidine. Dissolve 11.92 grams of decane-4,7-dione in 4.62 grams acetic acid and 100 mL methanol. Add 1.16 grams potassium hydroxide pellets. Stir to dissolve the potassium hydroxide. Cool the reaction mixture in an ice acetone bath at −15° C. Add 7.50 grams benzylamine followed immediately with 5.4 grams sodium cyanoborohydride in several portions. Let the reaction mixture warm up to room temperature over two days. Add 45 mL 4 N HCl drop-wise and stir for 30 minutes. Evaporate the reaction mixture under reduced pressure to remove most of the solvents. Dilute the residue with water, filter off some white solid, and extract the aqueous layer with ether. This ether solution contained 2,5-dipropylpyrrole. Cool the aqueous layer with an ice bath and add solid sodium hydroxide in small portions with stirring until pH-13. Dissolve the white solid above in this mixture. Extract with ether several times. Wash the combined ether solution with saturated brine, dry over anhydrous Na2SO4 and evaporate to give the crude 1-benzyl-2,5-dipropylpyrrolidine. The cis and trans isomers were separated on silica gel (5-10% EtOAc in hexanes with 1% Et3N). The slow eluting isomer was cis-1-benzyl-2,5-dipropylpyrrolidine. 1H NMR (CDCl3, 500 MHz) δ7.29-7.35 (m, 4H), 7.24-7.26 (m, 1H), 3.77 (s, 2H), 2.53-2.58 (m, 2H), 1.77-1.84 (m, 2H), 1.52-1.58 (m, 2H), 1.27-1.44 (m, 4H), 1.13-1.25 (m, 4H), 0.865 (t, J=7.2 Hz, 61).

Workup

  1. temperaturewarm up to room temperature over two days
  2. stirringstir for 30 minutes
  3. customEvaporate the reaction mixture under reduced pressure
  4. customto remove most of the solvents
  5. additionDilute the residue with water
  6. filtrationfilter off some white solid
  7. extractionextract the aqueous layer with ether
  8. temperatureCool the aqueous layer with an ice bath
  9. additionadd solid sodium hydroxide in small portions
  10. stirringwith stirring until pH-13
  11. dissolutionDissolve the white solid above in this mixture
  12. extractionExtract with ether several times
  13. washWash the combined ether solution with saturated brine
  14. dry with materialdry over anhydrous Na2SO4
  15. customevaporate

Sources & evidence

ORD record
ord-814e943a9e1a42c7a48e060132470c07
Source dataset
uspto-grants-2009_05
Patent number
US07528163B2

Reaction notes

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