Diethyl Ether → 4-[3-(1-Hydroxy-cyclohexyl)-indole-1-sulfonyl]-benzoic acid methyl ester

HRID 737008Notes

Reaction equation

HRID 737008 reaction equation
CCOCC.C1([Mg]Br)CC1.[CH3:11][O:12][C:13](=[O:33])[C:14]1[CH:19]=[CH:18][C:17]([S:20]([N:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25](I)=[CH:24]2)(=[O:22])=[O:21])=[CH:16][CH:15]=1.[C:34]1(=[O:40])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1>C1COCC1>[CH3:11][O:12][C:13](=[O:33])[C:14]1[CH:19]=[CH:18][C:17]([S:20]([N:23]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]([C:34]3([OH:40])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]3)=[CH:24]2)(=[O:22])=[O:21])=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 7967CyclohexanoneHCID 58974999Benzoic acid,4-[(3-iodo-1h-indol-1-yl)sulfonyl]-,methyl esterHCID 178418630HCID 178418630, compound

Product 1

HCID 589750254-[3-(1-Hydroxy-cyclohexyl)-indole-1-sulfonyl]-benzoic acid methyl esterYield 20.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Via addition funnel slowly add over 0.5 hours the 2M EtOEt solution of cyclopropyl magnesium bromide (2.16 g, 6.23 ml, 12.46 mmol, 1.1 eq) to the −78° C. THF solution (30 ml) of 4-(3-Iodo-indole-1-sulfonyl)-benzoic acid methyl ester (5 g, 11.33 mmol, 1.00 eq). Stir for 2 hours and then warm to 0° C. Stir for 0.5 hours. Recool to −10° C. and then slowly add a THF solution (3 ml) of cyclohexanone (1.298 g, 13.03 mmol, 1.15 eq). Stir for 15 min and warm to room temperature. Stir for 1.5 days. Quench reaction with saturated aqueous ammonium chloride, remove organics on rotovap, and add EtOAc to crude mix. Extract product into organics, separate organics, dry over MgSO4, and concentrate on rotovap to give crude product as an oil. Purify by silica gel chromatography to give 4-[3-(1-Hydroxy-cyclohexyl)-indole-1-sulfonyl]-benzoic acid methyl ester (948 mg, 20% yield).

Workup

  1. additionVia addition funnel
  2. stirringStir for 0.5 hours
  3. customRecool to −10° C.
  4. stirringStir for 15 min
  5. temperaturewarm to room temperature
  6. stirringStir for 1.5 days
  7. customQuench
  8. customreaction with saturated aqueous ammonium chloride
  9. customremove organics on rotovap
  10. additionadd EtOAc to crude
  11. additionmix
  12. customExtract product into organics, separate organics
  13. dry with materialdry over MgSO4
  14. concentrationconcentrate on rotovap
  15. customto give crude product as an oil
  16. customPurify by silica gel chromatography

Sources & evidence

ORD record
ord-3245f66f41e740c8bc780984c0056526
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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