Hydrochloric Acid → Ethyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-hydroxy-1H-indol-2-yl)-2,2-dimethylpropanoate

HRID 1975733Notes

Reaction equation

HRID 1975733 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].[Cl:5][C:6]1[CH:37]=[CH:36][C:9]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][C:16]([O:20]C)=[CH:17][CH:18]=3)[C:13]([S:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[C:12]2[CH2:27][C:28]([CH3:35])([CH3:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:8][CH:7]=1.Cl>ClCCl>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:10][N:11]2[C:19]3[C:14](=[CH:15][C:16]([OH:20])=[CH:17][CH:18]=3)[C:13]([S:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[C:12]2[CH2:27][C:28]([CH3:35])([CH3:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:36][CH:37]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6451240Aluminum(III) ChlorideHCID 19935666Ethyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-methoxy-1H-indol-2-yl)-2,2-dimethylpropanoate

Product 1

HCID 19935664Ethyl 3-(3-(tert-butylthio)-1-(4-chlorobenzyl)-5-hydroxy-1H-indol-2-yl)-2,2-dimethylpropanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Aluminum chloride (4.1 g; 30.7 mmol) was suspended in 9 mL t-butylthiol and cooled to 0° C. Ethyl 3-[1-(4-chlorobenzyl)-3-(1,1-dimethylethylthio)-5-methoxyindol-2-yl]-2,2-dimethylpropionate (5.0 g; 10.2 mmol), prepared as in step 3, in 12 mL dichloromethane was added and the reaction mixture was stirred at 0° C. for 10 min and then at ambient temperature for 3 hours. The reaction mixture was poured into ice and acidified with 10% aqueous HCl. The mixture was extracted three times with dichloromethane. The combined extracts were rinsed with brine, dried over magnesium sulfate and concentrated. The dark brown residue was filtered through silica gel eluting with 10% diethyl ether in dichloromethane. Evaporation of the solvent afforded ethyl 3-[1-(4-chlorobenzyl)-3-(1,1-dimethylethylthio)-5-hydroxyindol-2-yl]-2,2-dimethylpropionate. m.p. 151°-152° C. 1H NMR (300 MHz, DMSO-d6) δ1.10 (t, J=7 Hz, 3H), 1.12 (s, 6H), 1.20 (s, 9H), 3.19 (bs, 2H), 4.04 (q, J=7 Hz, 2H), 5.41 (s, 2H), 6.58 (dd, J=9, 3 Hz, 1H), 6.83 (d, J=9 Hz, 2H), 6.98 (d, J=3 Hz, 1H), 7.13 (d, J=9 Hz, 1H), 7.32 (d, J=9 Hz, 2H), 8.88 (s, 1H). MS (DCI/NH3) 474 (M+H)+.

Workup

  1. waitat ambient temperature for 3 hours
  2. additionThe reaction mixture was poured into ice
  3. extractionThe mixture was extracted three times with dichloromethane
  4. washThe combined extracts were rinsed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. filtrationThe dark brown residue was filtered through silica gel eluting with 10% diethyl ether in dichloromethane
  8. customEvaporation of the solvent

Sources & evidence

ORD record
ord-0af90b6bada64205ae30754985f78902
Source dataset
uspto-grants-1994_02
Patent number
US05288743

Reaction notes

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