5-Fluoro-1-(phenylsulfonyl)-1H-indole → 4-[(1-benzenesulfonyl-5-fluoro-1H-indol-2-yl)-hydroxy-methyl]4-propyl-piperidine-1-carboxylic acid tert-butyl ester

HRID 661567Notes

Reaction equation

HRID 661567 reaction equation
[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=3)[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]C(C)(C)C.[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][C:35]([CH:41]=[O:42])([CH2:38][CH2:39][CH3:40])[CH2:34][CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26]>C1COCC1>[C:25]([O:29][C:30]([N:32]1[CH2:37][CH2:36][C:35]([CH:41]([C:11]2[N:10]([S:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)(=[O:9])=[O:8])[C:18]3[C:13]([CH:12]=2)=[CH:14][C:15]([F:19])=[CH:16][CH:17]=3)[OH:42])([CH2:38][CH2:39][CH3:40])[CH2:34][CH2:33]1)=[O:31])([CH3:27])([CH3:28])[CH3:26]

Participants

5

Reactant 3

HCID 112888585-Fluoro-1-(phenylsulfonyl)-1H-indoleHCID 58017246Tert-butyl 4-formyl-4-propylpiperidine-1-carboxylateHCID 178418306HCID 178418306, compound

Product 1

HCID 666875264-[(1-benzenesulfonyl-5-fluoro-1H-indol-2-yl)-hydroxy-methyl]4-propyl-piperidine-1-carboxylic acid tert-butyl esterYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a −78° C. solution of 1-benzenesulfonyl-5-fluoro-1H-indole (539 mg, 1.96 mmol) in 30 mL THF, t-BuLi (1.5 mL, 2.54 mmol) was slowly added. The reaction mixture was stirred for 30 minutes, then a solution of 4-formyl-4-propyl-piperidine-1-carboxylic acid tert-butyl ester (500 mg, 1.96 mmol) in 5 mL THF was added. The reaction was allowed to stir for 2 hours at −78° C. and was then warmed to −20° C. and quenched with a saturated aqueous solution of ammonium chloride. The reaction mixture was extracted with ethyl acetate and the combined organic layers were washed with brine, dried (MgSO4), filtered and concentrated onto silica. The material was chromatographed over a 25 g Thomson column eluting with 20% ethyl acetate 80% hexanes to afford 4-[(1-benzenesulfonyl-5-fluoro-1H-indol-2-yl)-hydroxy-methyl]-4-propyl-piperidine-1-carboxylic acid tert-butyl ester (319 mg, 0.6 mmol) in a 53% yield as a beige foam.

Workup

  1. stirringto stir for 2 hours at −78° C.
  2. customquenched with a saturated aqueous solution of ammonium chloride
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated onto silica
  8. customThe material was chromatographed over a 25 g Thomson column
  9. washeluting with 20% ethyl acetate 80% hexanes

Sources & evidence

ORD record
ord-75c8c89deb244adcb06b5fe917f4400d
Source dataset
uspto-grants-2011_12
Patent number
US08084623B2

Reaction notes

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