Acetic Acid → 1-Carbamoyl-1H-indole-3-carboxylic acid benzyl ester

HRID 1052095Notes

Reaction equation

HRID 1052095 reaction equation
[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].ClS([N:26]=[C:27]=[O:28])(=O)=O.C(O)(=O)C>C1COCC1.CO.O>[CH2:1]([O:8][C:9]([C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]([C:27](=[O:28])[NH2:26])[CH:12]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 70918Chlorosulfonyl isocyanateHCID 8605861benzyl 1H-indole-3-carboxylate

Product 1

HCID 682844691-Carbamoyl-1H-indole-3-carboxylic acid benzyl ester

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1H-indole-3-carboxylic acid benzyl ester (3.5 g, 13.9 mmol) in THF (70 mL) at 5° C., was added NaH (60% in mineral oil, 557 mg, 13.9 mmol). The mixture was stirred at 5° C. for 30 min before slow dropwise addition of chlorosulfonyl isocyanate (2.42 mL, 27.9 mmol) maintaining the temperature between 5° C. and 10° C. The pale yellow solution was further stirred at RT for 3.5 h. Acetic acid (22.5 mL) was added (exothermic), and the resulting solution was stirred at RT for 1.5 h before addition of ice and water (100 mL). The white thick suspension was stirred at RT for 30 min and the precipitate was filtered-off, taken up in MeOH and filtered-off again to afford the desired compound. 1H-NMR (400 MHz, DMSO): δ (ppm) 8.64 (s, 1H), 8.29 (d, 1H), 8.04 (d, 1H), 7.90 (m, 2H), 7.50 (d, 2H), 7.42 (t, 2H), 7.36-7.30 (m, 3H), 5.38 (s, 2H).

Workup

  1. temperaturemaintaining the temperature between 5° C. and 10° C
  2. stirringThe white thick suspension was stirred at RT for 30 min

Sources & evidence

ORD record
ord-5cee28221b5b42609ce8edaa3194dc98
Source dataset
uspto-grants-2016_07
Patent number
US09388199B2

Reaction notes

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