Iodine → (2S-trans)-1-[(Benzyloxy)carbonyl]-4-cyclohexyl-2-pyrrolidinemethanol

HRID 280378Notes

Reaction equation

HRID 280378 reaction equation
[CH:1]1([C@H:7]2[CH2:11][NH:10][C@H:9]([CH2:12][OH:13])[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].[CH2:20]([O:27][C:28](Cl)=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.II>O1CCCC1.C(OCC)(=O)C.CCCCCC.O>[CH2:20]([O:27][C:28]([N:10]1[CH2:11][C@H:7]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)[CH2:8][C@H:9]1[CH2:12][OH:13])=[O:29])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

8

Reactant 4

HCID 807IodineHCID 10387Benzyl chloroformateHCID 11430Potassium CarbonateHCID 13648259(2S-trans)-4-cyclohexyl-2-pyrrolidinemethanol

Product 1

HCID 13648262(2S-trans)-1-[(Benzyloxy)carbonyl]-4-cyclohexyl-2-pyrrolidinemethanol

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a solution of (2S-trans)-4-cyclohexyl-2-pyrrol idinemethanol(45 g) in tetrahydrofuran (400 ml) was added potassium carbonate solution (18.7 g, 120 ml water and cooled to -2° C. (Benzyloxy)carbonyl chloride (37.7 ml) was added dropwise to the well stirred reaction mixture, keeping the inside temperature between -2° and 0° C. After the addition (20 minutes), the reaction mixture was stirred for 15 minutes at 0° C. and poured into crushed ice and water (500 ml). The organic layer was separated after saturation with sodium chloride and the aqueous phase was extracted with ethyl acetate (3×100 ml). The combined organic phase was washed with 5% hydrochloric acid (2×100 ml), water (1×100 ml) and brine (1×100 ml). Evaporation of the solvents after drying over anhydrous sodium sulfate furnished a colorless thick oil, 78.1 g. TLC showed a single spot at Rf =0.7 with very faint shadow at origin and at solvent front (silica gel, ethyl acetate-hexane, 4:1, UV and iodine). [α]D =-21.0°.

Workup

  1. additionwas added dropwise to the well
  2. customreaction mixture
  3. customthe inside temperature between -2° and 0° C
  4. additionAfter the addition (20 minutes)
  5. stirringthe reaction mixture was stirred for 15 minutes at 0° C.
  6. additionpoured
  7. customThe organic layer was separated after saturation with sodium chloride
  8. extractionthe aqueous phase was extracted with ethyl acetate (3×100 ml)
  9. washThe combined organic phase was washed with 5% hydrochloric acid (2×100 ml), water (1×100 ml) and brine (1×100 ml)
  10. customEvaporation of the solvents
  11. dry with materialafter drying over anhydrous sodium sulfate
  12. customfurnished a colorless thick oil, 78.1 g
  13. custom[α]D =-21.0°

Sources & evidence

ORD record
ord-2386be4f679d470492b0957ccc216de0
Source dataset
uspto-grants-1986_05
Patent number
US04588819

Reaction notes

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