Acetic Acid → HCID 86673792, compound

HRID 1527169Notes

Reaction equation

HRID 1527169 reaction equation
[H-].[Na+].[CH2:3]([O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][CH:11]=[C:10]2[CH:16]=[O:17])[CH:4]=[CH2:5].ClS([N:22]=[C:23]=[O:24])(=O)=O.C(O)(=O)C>C1COCC1.O>[CH2:3]([O:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([C:23]([NH2:22])=[O:24])[CH:11]=[C:10]2[CH:16]=[O:17])[CH:4]=[CH2:5]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 70918Chlorosulfonyl isocyanateHCID 86673791HCID 86673791, compound

Product 1

HCID 86673792HCID 86673792, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (60% in mineral oil, 352 mg, 8.79 mmol) in THF (12 mL) under nitrogen atmosphere at 5° C. was added a solution of 5-allyloxy-1H-indole-3-carbaldehyde (1.18 g, 5.86 mmol) in THF (28 mL) and the resulting mixture was stirred at 5° C. for 30 min before slow addition of chlorosulfonyl isocyanate (11.02 mL, 11.7 mmol) while maintaining the temperature between 5° C. and 10° C. The solution was further stirred at RT for 4 h, acetic acid (11 mL) was added and the solution was stirred at RT for 1 h. Ice cubes and water (100 mL) were added and the mixture was stirred at RT for 30 min. The solution was extracted twice with EtOAc and the combined organic extracts were dried over Na2SO4, filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (100% c-hexane to 100% EtOAc) to give the title compound. TLC, Rf (c-hexane/EtOAc 1:2)=0.36; MS (LC/MS): 245.1 [M+H]+, 267.0 [M+Na]+, 200.1 [M−CONH2]−; tR (HPLC conditions a): 2.95 min.

Workup

  1. temperaturewhile maintaining the temperature between 5° C. and 10° C
  2. stirringthe solution was stirred at RT for 1 h
  3. stirringthe mixture was stirred at RT for 30 min
  4. extractionThe solution was extracted twice with EtOAc
  5. dry with materialthe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash column chromatography on silica gel (100% c-hexane to 100% EtOAc)

Sources & evidence

ORD record
ord-1498f3767220411dbd84097ba719ad47
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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