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

HRID 1523078ノート

反応式

HRID 1523078 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-db4ed18af0a14fca9f73115a8fba24cc
出典データセット
uspto-grants-2015_07
特許番号
US09079853B2

反応ノート

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