Hydrochloric Acid → [6-Chloro-2-(4-chloro-benzoyl)-1H-indol-3-yl]-acetic acid ethyl ester

HRID 396575Notes

Reaction equation

HRID 396575 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([Cl:13])=[CH:9][C:8]=1[NH:14]S(C1C=CC(C)=CC=1)(=O)=O)[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:33][C:34]([C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)=[O:35].N12CCCN=C1CCCCC2.Cl>CN(C)C(=O)C.C(OC)(C)(C)C>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][C:6]1[C:7]2[C:8](=[CH:9][C:10]([Cl:13])=[CH:11][CH:12]=2)[NH:14][C:33]=1[C:34](=[O:35])[C:36]1[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=1)[CH3:2]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 68303p-Chlorophenacyl bromideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 53985536HCID 53985536, compound

Product 1

HCID 11057884[6-Chloro-2-(4-chloro-benzoyl)-1H-indol-3-yl]-acetic acid ethyl esterYield 81.4%

Reagents, catalysts & solvents 2

HCID 15413tert-Butyl methyl etherSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 3-[4-chloro-2-(toluene-4-sulfonylamino)-phenyl]-acrylic acid ethyl ester (3.00 g, 7.90 mmol) in N,N-dimethylacetamide (15.0 ml) was added potassium carbonate (2.18 g, 15.8 mmol) and 2-bromo-4′-chloroacetophenone (2.03 g, 8.69 mmol). The reaction was stirred 30 minutes and 1,8-diazabicyclo[5.4.0]undec-7-ene (3.54 ml, 23.7 mmol) was added. The reaction mixture was stirred one hour, poured into 1N hydrochloric acid (30 ml) and extracted with methyl t-butyl ether (2×30 ml). The organic extracts were dried with magnesium sulfate, filtered, and concentrated to provide a solid which was slurried in a mixture of methyl t-butyl ether and hexanes to afford [6-chloro-2-(4-chloro-benzoyl)-1H-indol-3-yl]-acetic acid ethyl ester (2.42 g, 81%). mp=186-188° C. 1H NMR (300 MHz, CDCl3) d 1.27 (t, 2, J=7.1), 3.80 (s, 2), 4.11 (q, 2, J=7.1), 7.15 (ddd, 1, J=8.5, 1.7, 0.5), 7.28-7.30 (m, 1), 7.48 (d, J=8.3), 7.54-7.57 (m, 1), 7.77 (d, 2, J=8.3), 9.16 (bs, 1). 13C NMR (75 MHz, CDCl3) d 15.42, 32.29, 62.45, 113.27, 117.60, 122.99, 123.23, 127.85, 130.12, 131.77, 133.61, 137.86, 138.13, 140.10, 172.45, 188.25. IR 3305, 1732, 1618, 1323 cm−1. Analysis calculated for C19H15Cl2NO3: C, 60.65; H, 4.02; N, 3.72. Found: C, 60.70; H, 3.97; N, 3.71.

Workup

  1. stirringThe reaction mixture was stirred one hour
  2. extractionextracted with methyl t-butyl ether (2×30 ml)
  3. dry with materialThe organic extracts were dried with magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto provide a solid which

Sources & evidence

ORD record
ord-c7312539905743ac9619abe9b3e0aca6
Source dataset
uspto-grants-2003_08
Patent number
US06608070B1

Reaction notes

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