Benzenesulfonyl fluoride → 4-(2-benzenesulfonyl-1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 130361Notes

Reaction equation

HRID 130361 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH:16]=[CH:17][N:18]3[CH3:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li]C(C)(C)C.[C:29]1([S:35](F)(=[O:37])=[O:36])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH:16]=[C:17]([S:35]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)(=[O:37])=[O:36])[N:18]3[CH3:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 67779Benzenesulfonyl fluorideHCID 597305564-(1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester2×HCID 178418306HCID 178418306, compound

Product 1

HCID 597305584-(2-benzenesulfonyl-1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-75 °C

Procedure

To a −75° C. solution of 4-(1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester compound 3-1 (330 mg, 1.05 mmol) in THF (25 mL) was slowly added t-BuLi (1.2 mL, 2.1 mmol). The reaction mixture was stirred for 30 minutes at −75° C. then warmed in an ice bath for 15 min. The reaction was re-cooled to −75° C. and benzenesulfonyl fluoride was added (0.2 mL, 1.6 mmol). The reaction was stirred cold for 1.5 h at which time the ice bath was removed and the reaction was allowed to warm to room temperature (45 min.). The reaction was quenched with a saturated solution of ammonium chloride (55 mL) and extracted with ethyl acetate (3×20 mL). The combined ethyl acetate layers were washed with brine (25 mL), dried (MgSO4), filtered and concentrated to afford a yellow oil. The oil was chromatographed over silica eluting with hexanes/ethyl acetate (4:1) to afford 190 mg (40%) of 4-(2-benzenesulfonyl-1-methyl-1H-indol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (3-2).

Workup

  1. customTo a −75° C.
  2. temperaturethen warmed in an ice bath for 15 min
  3. temperatureThe reaction was re-cooled to −75° C.
  4. customwas removed
  5. temperatureto warm to room temperature (45 min.)
  6. customThe reaction was quenched with a saturated solution of ammonium chloride (55 mL)
  7. extractionextracted with ethyl acetate (3×20 mL)
  8. washThe combined ethyl acetate layers were washed with brine (25 mL)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto afford a yellow oil
  13. customThe oil was chromatographed over silica eluting with hexanes/ethyl acetate (4:1)

Sources & evidence

ORD record
ord-8e63a46abf334a8a9d85aeccb590722a
Source dataset
uspto-grants-2008_06
Patent number
US07381739B2

Reaction notes

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