2-Fluorobenzene-1-sulfonyl fluoride → 4-(4-Tert-butoxycarbonyl-piperazin-1-yl)-2-(2-fluoro-benzenesulfonyl)-indole-1-carboxylic acid tert-butyl ester

HRID 130360Notes

Reaction equation

HRID 130360 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([N:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]3)[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.[F:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[S:42](F)(=[O:44])=[O:43]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[C:12]([N:17]3[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:21][CH2:22]3)[CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[S:42]([C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=1[F:35])(=[O:44])=[O:43])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 141952602-Fluorobenzene-1-sulfonyl fluorideHCID 597305544-(4-Tert-butoxycarbonyl-piperazin-1-yl)-indole-1-carboxylic acid tert-butyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 597305514-(4-Tert-butoxycarbonyl-piperazin-1-yl)-2-(2-fluoro-benzenesulfonyl)-indole-1-carboxylic acid tert-butyl esterYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a −75° C. solution of 4-(4-tert-butoxycarbonyl-piperazin-1-yl)-indole-1-carboxylic acid tert-butyl ester 2 (500 mg, 1.25 mmol) in THF (25 mL) was slowly added t-BuLi (1.47 mL, 2.5 mmol). The reaction mixture was stirred for 30 minutes at which time 2-fluoro-benzenesulfonyl fluoride 2a (222 mg, 1.5 mmol) was added. The reaction was stirred for 1.5 h at which time the ice bath was removed and the reaction was allowed to warm over 45 min. The reaction mixture was quenched with a saturated solution of ammonium chloride (55 mL). The mixture was then extracted with ethyl acetate (3×20 mL). The combined ethyl acetate layers were washed with brine (25 mL). The organic layer was dried (MgSO4), filtered, and concentrated to afford a yellow oil. The oil was chromatographed over silica eluting with hexane:ethyl acetate (17:3) to afford 300 mg (43%) of 4-(4-tert-butoxycarbonyl-piperazin-1-yl)-2-(2-fluoro-benzenesulfonyl)-indole-1-carboxylic acid tert-butyl ester (1-3).

Workup

  1. customTo a −75° C.
  2. additionwas added
  3. customwas removed
  4. temperatureto warm over 45 min
  5. customThe reaction mixture was quenched with a saturated solution of ammonium chloride (55 mL)
  6. extractionThe mixture was then extracted with ethyl acetate (3×20 mL)
  7. washThe combined ethyl acetate layers were washed with brine (25 mL)
  8. dry with materialThe organic layer was dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto afford a yellow oil
  12. customThe oil was chromatographed over silica eluting with hexane:ethyl acetate (17:3)

Sources & evidence

ORD record
ord-7858d983db254bbaa3689662ece43e79
Source dataset
uspto-grants-2008_06
Patent number
US07381739B2

Reaction notes

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