Methanol → 4-(1-(4-chloro-2-methoxyphenyl)-3-(hydroxymethyl)-1H-pyrrol-2-yl)-3-methylbenzamide

HRID 238407Notes

Reaction equation

HRID 238407 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][C:21]=3[O:27][CH3:28])[CH:12]=[CH:13][C:14]=2[C:15](OCC)=[O:16])=[C:6]([CH3:29])[CH:5]=1)(=[O:3])[NH2:2].CC(C[AlH]CC(C)C)C.CCOC(C)=O.CO>C1(C)C=CC=CC=1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([N:11]2[CH:12]=[CH:13][C:14]([CH2:15][OH:16])=[C:10]2[C:7]2[CH:8]=[CH:9][C:4]([C:1]([NH2:2])=[O:3])=[CH:5][C:6]=2[CH3:29])=[C:21]([O:27][CH3:28])[CH:22]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 14487Diisobutylaluminum hydrideHCID 67176148ethyl 2-(4-carbamoyl-2-methylphenyl)-1-(4-chloro-2-methoxyphenyl)-1H-pyrrole-3-carboxylate

Product 1

HCID 671752774-(1-(4-chloro-2-methoxyphenyl)-3-(hydroxymethyl)-1H-pyrrol-2-yl)-3-methylbenzamideYield 40.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of ethyl 2-(4-carbamoyl-2-methylphenyl)-1-(4-chloro-2-methoxyphenyl)-1H-pyrrole-3-carboxylate (1.2 g, 2.9 mmol) in anhydrous toluene (50 mL) was cooled to −78° C., DIBAL-H (1.0 mol/L, 14.5 mL) was added dropwise, and the reaction mixture was stirred at this temperature for two hours. TLC (EtOAc: MeOH=10:1) indicated that the starting material was consumed. Saturated aqueous NH4Cl solution was added to quench the reaction, and the mixture was filtered. The filtrate was extracted with EtOAc (20 mL×3), and the combined organic layer was washed with brine (20 mL), dried over Na2SO4, filtered, concentrated, and purified by column chromatography to give the titled compound (430 mg, yield: 40.2%). 1H NMR (CD3OD 300 MHz TMS): δ 7.63 (s, 1H), 7.55 (m, 1H), 7.21 (d, J=7.8 Hz, 1H), 7.03 (d, J=8.1 Hz, 1H), 6.95 (d, J=2.1 Hz, 1H), 6.82-6.87 (m, 2H), 6.43 (d, J=3.0 Hz, 1H), 4.38 (d, J=11.7 Hz, 1H), 4.27 (d, J=11.7 Hz, 1H), 3.60 (s, 3H), 2.10 (s, 3H).

Workup

  1. customwas consumed
  2. additionSaturated aqueous NH4Cl solution was added
  3. customto quench
  4. customthe reaction
  5. filtrationthe mixture was filtered
  6. extractionThe filtrate was extracted with EtOAc (20 mL×3)
  7. washthe combined organic layer was washed with brine (20 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. custompurified by column chromatography

Sources & evidence

ORD record
ord-30df0e45755e487ea12f0f019b679fea
Source dataset
uspto-grants-2014_02
Patent number
US08642628B2

Reaction notes

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