Pentane → HCID 21021922, compound

HRID 1793870Notes

Reaction equation

HRID 1793870 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]C(C)(C)C.CCCCC.[F:27][C:28]1[CH:33]=[CH:32][C:31]([S:34](F)(=[O:36])=[O:35])=[CH:30][CH:29]=1.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[S:34]([C:31]1[CH:32]=[CH:33][C:28]([F:27])=[CH:29][CH:30]=1)(=[O:36])=[O:35])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 5

HCID 8003PentaneHCID 25517Ammonium ChlorideHCID 30819424-Fluorobenzenesulfonyl fluorideHCID 35329801-Boc-indoleHCID 178418306HCID 178418306, compound

Product 1

HCID 21021922HCID 21021922, compoundYield 43.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 1-indole carboxylic acid tert-butyl ester (1.88 g, 8.65 mmol) in 100 mL of anhydrous THF was cooled to −78° C. in a dry ice/acetone bath under an argon gas blanket. A fresh commercial (Aldrich) 1.7 M solution of t-BuLi in pentane (10.2 mL, 17.3 mmol, 2.0 eq) was slowly added to the stirring mixture via syringe. During the addition, the solution turned from a light amber-red color to a dark, orange-burgundy color. After the addition was complete, the reaction mixture was allowed to stir for 45 minutes at −78° C. and then 4-fluorobenzenesulfonyl fluoride was slowly added to the reaction mixture while carefully maintaining an internal temperature of <−65° C. The reaction mixture was kept at −75 to −78° C. for a period of 20 minutes after the addition was complete then was allowed to warm to room temperature, where it remained for 2 h. The reaction mixture was poured into 500 mL of saturated NH4Cl solution, diluted with 500 mL of EtOAc and mixed well. The pale, amber-orange organic layer was separated, washed with brine and dried over anhydrous magnesium sulfate. Evaporation of the solvent gave a dark amber oil which was silica-gel chromatographed, gradient eluting with 10% EtOAc/Hexane followed by CHCl3 to give 1.40 g, 3.73 mmol, 43.1% yield of the 2-(4-Fluoro-benzenesulfonyl)-indole-1-carboxylic acid tert-butyl ester as an amber oil which solidified on standing to a pale reddish-tan solid which had a melting point range of 88–93° C.

Workup

  1. additionDuring the addition
  2. additionAfter the addition
  3. temperaturewhile carefully maintaining an internal temperature of <−65° C
  4. waitThe reaction mixture was kept at −75 to −78° C. for a period of 20 minutes
  5. additionafter the addition
  6. temperatureto warm to room temperature
  7. waitwhere it remained for 2 h
  8. additionmixed well
  9. customThe pale, amber-orange organic layer was separated
  10. washwashed with brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customEvaporation of the solvent
  13. customgave a dark amber oil which
  14. customchromatographed
  15. washgradient eluting with 10% EtOAc/Hexane

Sources & evidence

ORD record
ord-f21b2fcfd36e480eaa3b32f706511d35
Source dataset
uspto-grants-2006_04
Patent number
US07022708B2

Reaction notes

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