Pyrrolidine → 1-[2-Hydroxy-5-(pyrrolidine-1-carbonyl)-phenyl]-ethanone

HRID 1788412Notes

Reaction equation

HRID 1788412 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[OH:13])[C:7]([OH:9])=O)(=[O:3])[CH3:2].CC[N:16]([CH:20]([CH3:22])C)[CH:17]([CH3:19])C.N1CCCC1>CN(C=O)C>[OH:13][C:12]1[CH:11]=[CH:10][C:6]([C:7]([N:16]2[CH2:17][CH2:19][CH2:22][CH2:20]2)=[O:9])=[CH:5][C:4]=1[C:1](=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 81531DiisopropylethylamineHCID 91792453-Acetyl-4-hydroxybenzoic acid

Product 1

HCID 576031221-[2-Hydroxy-5-(pyrrolidine-1-carbonyl)-phenyl]-ethanoneYield 62.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 500 mg (2.8 mmol) of 3-acetyl-4-hydroxy-benzoic acid in 5 mL of DMF, 721.6 μL (4.2 mmol) of TFA-OPfp and 731.5 μL (4.2 mmol) of DIEA were added. The clear solution was stirred at room temperature for 15 minutes, then 467.5 μL (5.6 mmol) of pyrrolidine was added. The mixture was stirred for another hour and was then evaporated to dryness. The oily residue was taken up in 50 mL water-50 mL ethyl acetate mixture, the EtOAc phase was separated, washed twice with 1 M HCl, water, saturated NaHCO3, brine and was dried with Na2SO4. The EtOAc was evaporated; the oil was purified on an open silica gel column using a toluene/ethyl acetate gradient containing 5% acetic acid to yield 410 mg (51%) Compound 18.

Workup

  1. stirringThe mixture was stirred for another hour
  2. customwas then evaporated to dryness
  3. customthe EtOAc phase was separated
  4. washwashed twice with 1 M HCl, water, saturated NaHCO3, brine
  5. dry with materialwas dried with Na2SO4
  6. customThe EtOAc was evaporated
  7. customthe oil was purified on an open silica gel column
  8. additioncontaining 5% acetic acid

Sources & evidence

ORD record
ord-909554a9c9e143c28f84455eeb665bc7
Source dataset
uspto-grants-2009_03
Patent number
US07511145B2

Reaction notes

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