Hydrochloric Acid → 1-Ethyl-5-methyl-2-oxo-3-(3,4,5-trimethoxybenzyl)indolin-3-yl benzoate

HRID 1523078Notes

Reaction equation

HRID 1523078 reaction equation
[C:1]([O:9][CH:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:19])[CH:17]=2)[N:12]([CH2:20][CH3:21])[C:11]1=[O:22])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:33][O:34][C:35]1[CH:36]=[C:37]([CH:40]=[C:41]([O:45][CH3:46])[C:42]=1[O:43][CH3:44])[CH2:38]Cl.Cl>C(OCC)(=O)C>[C:1]([O:9][C:10]1([CH2:38][C:37]2[CH:40]=[C:41]([O:45][CH3:46])[C:42]([O:43][CH3:44])=[C:35]([O:34][CH3:33])[CH:36]=2)[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH3:19])[CH:17]=2)[N:12]([CH2:20][CH3:21])[C:11]1=[O:22])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 774485-(Chloromethyl)-1,2,3-trimethoxybenzeneHCID 2733832Lithium HexamethyldisilazideHCID 904159121-Ethyl-5-methyl-2-oxoindolin-3-yl benzoate

Product 1

HCID 863006811-Ethyl-5-methyl-2-oxo-3-(3,4,5-trimethoxybenzyl)indolin-3-yl benzoate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To an oven dried flask cooled under argon equipped with a stir bar was added 1-ethyl-5-methyl-2-oxoindolin-3-yl benzoate (0.05 grams, 0.17 mmol, 0.5 M in toluene). While stirring at room temperature LiHMDS (0.3 mL, 0.3 mmol, 1.0 M, purchased from Fisher Scientific) was added. After approximately ten minutes a solution of 3,4,5 trimethoxybenzyl chloride (0.0553 grams, 0.26 mmol, purchased from Aldrich, 0.5 M in anhydrous DMF) was added. The reaction continued to stir overnight. The next day the reaction was acidified with 0.1M HCl, diluted with ethyl acetate and the two layers were separated. The aqueous layer was salted out and washed twice more with ethyl acetate. The combined organic solution was dried with sodium sulfate, filtered and concentrated. Purification was done on a Teledyne ISCO with silica gel using a hexanes/ethyl acetate gradient. This was followed by a subsequent reverse phase purification using Teledyne ISCO with a C18 column and a water with 0.1% formic acid, acetonitrile gradient. Yield (20%) 1H-NMR δ 8.05 (d, 2H), 7.57 (dd, 1H), 7.43 (m, 2H), 7.08 (d, 1H), 6.97 (s, 1H), 6.62 (d, 1H), 6.17 (s, 2H), 3.78 (s, 3H), 3.76 (m, 1H), 3.68 (s, 6H), 3.53 (m, 1H), 3.29 (d, 1H), 3.24 (d, 1H), 2.28 (s, 3H), 1.00 (t, 3H). Calculated mass for C28H29NO6, 475.20. Observed 498.2 (M+Na).

Workup

  1. customTo an oven dried flask
  2. temperaturecooled under argon
  3. customequipped with a stir bar
  4. additionwas added
  5. customthe two layers were separated
  6. washwashed twice more with ethyl acetate
  7. dry with materialThe combined organic solution was dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification
  11. customThis was followed by a subsequent reverse phase purification
  12. customYield (20%) 1H-NMR δ 8.05 (d, 2H), 7.57 (dd, 1H), 7.43 (m, 2H), 7.08 (d, 1H), 6.97 (s, 1H), 6.62 (d, 1H), 6.17 (s, 2H), 3.78 (s, 3H), 3.76 (m, 1H), 3.68 (s, 6H), 3.53 (m, 1H), 3.29 (d, 1H), 3.24 (d, 1H), 2.28 (s, 3H), 1.00 (t, 3H)

Sources & evidence

ORD record
ord-db4ed18af0a14fca9f73115a8fba24cc
Source dataset
uspto-grants-2015_07
Patent number
US09079853B2

Reaction notes

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