1-Bromo-3-chloropropane → 5-(3-Chloro-propoxy)-1H-indole-2-carboxylic acid ethyl ester

HRID 132816

Reaction equation

HRID 132816 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].Br[CH2:17][CH2:18][CH2:19][Cl:20].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[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][CH2:17][CH2:18][CH2:19][Cl:20])=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 11430Potassium CarbonateHCID 90677Ethyl 5-hydroxy-1H-indole-2-carboxylate

Product 1

HCID 451123565-(3-Chloro-propoxy)-1H-indole-2-carboxylic acid ethyl esterYield 74%

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

A mixture of ethyl-5-hydroxyindole-2-carboxylate (purchased at Biosynth, Ref H-6350, 15 g, 1.0 eq.), 1-bromo-3-chloropropane (8.8 mL, 1.2 eq.) and potassium carbonate (12.12 g, 1.2 eq.) in butanone (200 mL) was stirred 4 days at reflux. The reaction mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water and brine, evaporated in vacuo and purified on silica, eluting with a 19:1 to 2:1 gradient of cyclohexane/ethyl acetate to yield 15.3 g (74%) of the desired product as light yellow solid. MS (m/e): 282.5 (MH+, 100%).

Workup

  1. temperatureat reflux
  2. customThe reaction mixture was partitioned between ethyl acetate and water
  3. extractionThe aqueous layer was extracted with ethyl acetate
  4. washThe combined organic layers were washed with water and brine
  5. customevaporated in vacuo
  6. custompurified on silica
  7. washeluting with a 19:1 to 2:1 gradient of cyclohexane/ethyl acetate

Sources & evidence

ORD record
ord-f255e45802724c42866eefe1e752fc19
Source dataset
uspto-grants-2008_06
Patent number
US07388095B2

Linked notes

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