1,1'-(Azodicarbonyl)dipiperidine → 5-(1-isopropyl-pyrrolidin-3-yloxy)-1H-indole-2-carboxylic acid ethyl ester

HRID 901087Notes

Reaction equation

HRID 901087 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([OH:15])=[CH:10][CH:9]=2)=[O:5])[CH3:2].[CH:16]([N:19]1[CH2:23][CH2:22][CH:21](O)[CH2:20]1)([CH3:18])[CH3:17].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1COCC1>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH:21]1[CH2:22][CH2:23][N:19]([CH:16]([CH3:18])[CH3:17])[CH2:20]1)=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 90677Ethyl 5-hydroxy-1H-indole-2-carboxylateHCID 113095221-Isopropyl-3-pyrrolidinol

Product 1

HCID 670733165-(1-isopropyl-pyrrolidin-3-yloxy)-1H-indole-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 3.08 g (15 mmol) 5-hydroxy-1H-indole-2-carboxylic acid ethyl ester, 2.51 g (20 mmol) 1-isopropyl-3-pyrrolidinol and 8.7 ml (30 mmol) tri-N-butyl phosphine in 75 ml was treated at room temperature with 7.57 g (30 mmol) 1,1′-(azodicarbonyl)-dipiperidine in 75 ml THF. The mixture was allowed to stir for a prolonged period of time and subsequently evaporated to dryness. The residue was suspended in 40 ml DCM/n-heptane 1/1, filtered and again washed with 40 ml DCM/n-heptane 1/1. The filtrate was evaporated and purified on silica eluting with a gradient of DCM/2N NH3 in methanol 99/1 to DCM/2N NH3 in methanol 93/7. The product fractions were evaporated and the residue was titurated with diethyl ether to yield after filtration, washing and drying of the residue at 50° C. under vacuum 2.1 g (44%) of the title compound as off-white solid. MS (m/e): 317.1 (MH+, 100%).

Workup

  1. customsubsequently evaporated to dryness
  2. filtrationfiltered
  3. washagain washed with 40 ml DCM/n-heptane 1/1
  4. customThe filtrate was evaporated
  5. custompurified on silica eluting with a gradient of DCM/2N NH3 in methanol 99/1 to DCM/2N NH3 in methanol 93/7
  6. customThe product fractions were evaporated
  7. customto yield
  8. filtrationafter filtration
  9. washwashing
  10. dry with materialdrying of the residue at 50° C. under vacuum 2.1 g (44%) of the title compound as off-white solid

Sources & evidence

ORD record
ord-4b574b0f8cd9452fb39056e7198a2fb6
Source dataset
uspto-grants-2008_04
Patent number
US07361682B2

Reaction notes

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