Tributylphosphine → 6-(1-Isopropyl-pyrrolidin-3-yloxy)-1H-indole-2-carboxylic acid ethyl ester

HRID 901094Notes

Reaction equation

HRID 901094 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[C:10]([OH:15])[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].C(P(CCCC)CCCC)CCC.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][CH:11]=[C:10]([O:15][CH:21]1[CH2:22][CH2:23][N:19]([CH:16]([CH3:18])[CH3:17])[CH2:20]1)[CH:9]=2)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 113095221-Isopropyl-3-pyrrolidinolHCID 18459473HCID 18459473, compound

Product 1

HCID 692832026-(1-Isopropyl-pyrrolidin-3-yloxy)-1H-indole-2-carboxylic acid ethyl esterYield 100%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 1 g (4.8 mmol) ethyl-6-hydroxyindole-2-carboxylate (Journal of the American Chemical Society (1967), 89(13), 3349-50), 0.81 g (6.3 mmol) 1-isopropyl-3-pyrrolidinol, 2.83 ml (11 mmol) tri-n-butyl-phosphine and 2.56 g (9.75 mmol) 1,1′azodicarbonyl-dipiperidine in 50 ml THF was stirred at room temperature for 16 h. The suspension was filtered and the filtrated evaporated to dryness. The residue was purified with column chromatography on silica eluting with a gradient from DCM/2N NH3 in MeOH 99/1 to 19/1. The product containing fractions were combined and evaporated to dryness to yield a brown oil which was crystallized from diethyl ether and heptane to afford 0.5 g of brownish crystals (MS (m/e): 317.1 (MH+, 100%)). and after evaporation of the filtrate 0.6 g of slightly impure product which was used without further purification in the consecutive step.

Workup

  1. filtrationThe suspension was filtered
  2. customthe filtrated evaporated to dryness
  3. customThe residue was purified with column chromatography on silica eluting with a gradient from DCM/2N NH3 in MeOH 99/1 to 19/1
  4. additionThe product containing fractions
  5. customevaporated to dryness
  6. customto yield a brown oil which
  7. customwas crystallized from diethyl ether and heptane

Sources & evidence

ORD record
ord-c2c64c25509f44ceab9bc34fd0b56ecc
Source dataset
uspto-grants-2008_04
Patent number
US07361682B2

Reaction notes

Loading…