4-Fluoroiodobenzene → HCID 10686998, compound

HRID 481335Notes

Reaction equation

HRID 481335 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][C:13]([OH:15])=[O:14].[F:16][C:17]1[CH:22]=[CH:21][C:20](I)=[CH:19][CH:18]=1.C([O-])([O-])=O.[K+].[K+].CN1CCCC1=O>O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:20]1[CH:21]=[CH:22][C:17]([F:16])=[CH:18][CH:19]=1)[CH:6]=[C:5]2[CH2:11][CH2:12][C:13]([OH:15])=[O:14]

Participants

6

Reactant 4

HCID 96054-FluoroiodobenzeneHCID 11430Potassium CarbonateHCID 13387N-methyl-2-pyrrolidoneHCID 1857801H-Indole-3-propanoic acid, 5-chloro-

Product 1

HCID 10686998HCID 10686998, compoundYield 104.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
165 °C

Procedure

A mixture of 3-(5-chloro-3-1H-indolyl)propanoic acid (17.5 g, 0.078 mol), 4-fluoroiodobenzene (20.8 g, 0.094 mol), Cul (2.4 g), K2CO3 (21.6 g, 0.16 mol) and N-methyl-2-pyrrolidone (0.20 L) was heated at 165° C. for 7 h. The reaction mixture was cooled to room temperature and water (0.25 L) was added. After acidification with concentrated hydrochloric acid, the mixture was extracted with diethyl ether (2×0.30 L) . The combined organic phases were washed with brine (3×0.40 L) and dried (Na2SO4). Evaporation of the solvents afforded crude 3-[5-chloro-1-(4-fluorophenyl)-3-1H-indolyl]propanoic acid (26 g) as an oil. The oil was dissolved in dry diethyl ether and added to a suspension of lithium aluminum hydride (15 g, 0.40 mol) in dry diethyl ether (0.20 L) over 30 min. After reflux for further 2 h the reaction mixture was cooled to 0° C. and carefully treated with water (15 ml), 4N aqueous NaOH (15 ml) and then water (75 mL). The resulting mixture was filtered and dried (Na2SO4). Evaporation of the solvents afforded the title compound (1a) as an oil (17.6 g, 74%). An analytical sample was crystallized from heptane: mp. 67°-69° C.; 1H NMR (CDCl3) δ 1.55 (broad s, 1 H), 2.00 (qui, 2 H), 2.90 (t, 2 H), 3.75 (t, 2 H), 7.10 (s, 1 H), 7.15 (broad d, 1 H), 7.20 (t, 2 H), 7.35 (d, 1 H), 7.40 (dd, 2 H), 7.60 (broad s,1 H). Anal. (C17H15ClFNO) C, H, N.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionAfter acidification with concentrated hydrochloric acid, the mixture was extracted with diethyl ether (2×0.30 L)
  3. washThe combined organic phases were washed with brine (3×0.40 L)
  4. dry with materialdried (Na2SO4)
  5. customEvaporation of the solvents

Sources & evidence

ORD record
ord-6e4bb680ca5c404ab5aed0c8378efd05
Source dataset
uspto-grants-1998_08
Patent number
US05789404

Reaction notes

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