HCID 17604146, compound → HCID 46841137, compound

HRID 1846322Notes

Reaction equation

HRID 1846322 reaction equation
[Si]([O:8][CH2:9][CH2:10][O:11][C:12]1[C:19]([CH3:20])=[CH:18][C:15]([CH:16]=O)=[CH:14][C:13]=1[CH3:21])(C(C)(C)C)(C)C.[NH2:22][C:23]1[CH:41]=[CH:40][CH:39]=[CH:38][C:24]=1[C:25]([NH:27][C:28]1[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][CH:29]=1)=[O:26]>CCO>[OH:8][CH2:9][CH2:10][O:11][C:12]1[C:13]([CH3:21])=[CH:14][C:15]([C:16]2[N:27]([C:28]3[CH:37]=[CH:36][C:31]([C:32]([O:34][CH3:35])=[O:33])=[CH:30][CH:29]=3)[C:25](=[O:26])[C:24]3[C:23](=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:22]=2)=[CH:18][C:19]=1[CH3:20]

Participants

4

Reactant 2

HCID 17604146HCID 17604146, compoundHCID 866219154-(2-(Tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde

Product 1

HCID 46841137HCID 46841137, compoundYield 34.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Isatoic anhydride (4.0 g, 24.5 mmol) and methyl 4-aminobenzoate were combined and heated at 140° C. for 4 hours. The reaction was cool to room temperature and purified by flash chromatography on silica gel, eluting with 90-100% CH2Cl2 in heptane, to afford methyl 4-(2-aminobenzamido)benzoate (5.2 g, 78%). 4-(2-(tert-butyldimethylsilyloxy)ethoxy)-3,5-dimethylbenzaldehyde (1.0 g, 3.30 mmol) and anhydrous CuCl2 (1.3 g, 9.90 mmol) were added to a solution of methyl 4-(2-aminobenzamido)benzoate (0.900 g, 3.30 mmol) in anhydrous EtOH (70 mL) and heated to reflux for 6 hours, before being cooled to room temperature and concentrated in vacuo. Purification by flash chromatography on silica gel, eluting with 5% MeOH in CH2Cl2, followed by further purification on silica gel, eluting with 30-100% EtOAc in heptane, afforded the title compound as a white solid (0.500 g, 34%). 1H-NMR (300 MHz, DMSO-d6): δ 8.18 (dd, J=7.9, 1.1 Hz, 1H), 7.88-7.93 (m, 3H), 7.75 (d, J=6.7 Hz, 1H), 7.57-7.62 (m, 1H), 7.50 (d, J=8.5 Hz, 2H), 7.03 (s, 2H), 4.82 (t, J=5.5 Hz, 1H), 3.84 (s, 3H), 3.60-3.72 (m, 4H), 2.07 (s, 6H). MS (APCI) m/z: 445 (M+H)+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 6 hours
  3. concentrationconcentrated in vacuo
  4. customPurification by flash chromatography on silica gel
  5. washeluting with 5% MeOH in CH2Cl2
  6. customfollowed by further purification on silica gel
  7. washeluting with 30-100% EtOAc in heptane

Sources & evidence

ORD record
ord-53a5daaca91348fca91bedcb369ab828
Source dataset
uspto-grants-2015_02
Patent number
US08952021B2

Reaction notes

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