Acetic Acid → 1,2-dibenzyl 1-tert.butyl 4-methyl-1-(4-pyrrolidinylbut-2-yn-1-yl)-1,1,2(R)-pentanetricarboxylate

HRID 1464360Notes

Reaction equation

HRID 1464360 reaction equation
[CH3:1][CH:2]([CH3:36])[CH2:3][C@@H:4]([C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])[C:5]([CH2:23][C:24]#[CH:25])([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7].[NH:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1.C=O.[C:44](O)(=O)C>O1CCOCC1>[CH3:1][CH:2]([CH3:36])[CH2:3][C@@H:4]([C:26]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:27])[C:5]([CH2:23][C:24]#[C:25][CH2:44][N:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1)([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 31268PyrrolidineHCID 867477771,2-dibenzyl 1-tert.butyl 4-methyl-1-(prop-2-yn-1-yl)-1,1,2(R)-pentanetricarboxylate

Product 1

HCID 867477781,2-dibenzyl 1-tert.butyl 4-methyl-1-(4-pyrrolidinylbut-2-yn-1-yl)-1,1,2(R)-pentanetricarboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 0.501 g of 1,2-dibenzyl 1-tert.butyl 4-methyl-1-(prop-2-yn-1-yl)-1,1,2(R)-pentanetricarboxylate, 0.17 ml of pyrrolidine, 0.083 g of paraformaldehyde, 0.39 ml of glacial acetic acid and 0.004 g of cuprous chloride in 7 ml of dioxan was stirred at room temperature under a nitrogen atmosphere for 15 minutes and then heated to reflux for 2 hours. The mixture was then stirred at room temperature for a further 2 hours and evaporated, and the residue was partitioned between water and dichloromethane. The pH of the aqueous phase was adjusted to 10 by the addition of ammonium hydroxide and the dichloromethane layer was separated. The aqueous phase was extracted with three portions of dichloromethane and the combined extracts were washed with water, dried over anhydrous magnesium sulfate and evaporated to give a brown oil which was purified by flash chromatography on silica gel using ethyl acetate/hexane (4:1) for the elution. There was obtained 0.489 g of 1,2-dibenzyl 1-tert.butyl 4-methyl-1-(4-pyrrolidinylbut-2-yn-1-yl)-1,1,2(R)-pentanetricarboxylate in the form of a colorless oil; MS 576 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 hours
  3. stirringThe mixture was then stirred at room temperature for a further 2 hours
  4. customevaporated
  5. customthe residue was partitioned between water and dichloromethane
  6. additionThe pH of the aqueous phase was adjusted to 10 by the addition of ammonium hydroxide
  7. customthe dichloromethane layer was separated
  8. extractionThe aqueous phase was extracted with three portions of dichloromethane
  9. washthe combined extracts were washed with water
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customevaporated
  12. customto give a brown oil which
  13. customwas purified by flash chromatography on silica gel
  14. washfor the elution

Sources & evidence

ORD record
ord-4bd970ec871f439dbc5c714acbdf11b6
Source dataset
uspto-grants-1994_04
Patent number
US05304549

Reaction notes

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