N-[4-(3-Methylbutoxy)-2-nitrophenyl]-2-(3-methoxyphenoxy)acetamide → N-[2-Amino-4-(3-methylbutoxy)phenyl]-2-(3-methoxyphenoxy)acetamide

HRID 537294Notes

Reaction equation

HRID 537294 reaction equation
[CH3:1][CH:2]([CH3:28])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:24])[CH2:14][O:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=2)=[C:8]([N+:25]([O-])=O)[CH:7]=1>[Pd].CCO>[NH2:25][C:8]1[CH:7]=[C:6]([O:5][CH2:4][CH2:3][CH:2]([CH3:28])[CH3:1])[CH:11]=[CH:10][C:9]=1[NH:12][C:13](=[O:24])[CH2:14][O:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH3:23])[CH:17]=1

Participants

4

Reactant 1

HCID 86689283N-[4-(3-Methylbutoxy)-2-nitrophenyl]-2-(3-methoxyphenoxy)acetamide

Product 1

HCID 86689284N-[2-Amino-4-(3-methylbutoxy)phenyl]-2-(3-methoxyphenoxy)acetamideYield 98%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A 350 mL hydrogenation vessel was charge with nitroarene 48b (15.0 g, 38.6 mmol) and EtOH (150 mL). To the resultant suspension was added 10% Pd/C (1.4 g). The mixture was hydrogenated on a Parr shaker at 58 psi overnight. The reduction was incomplete as analyzed by HPLC and contained a large amount of ppt mixed with the catalyst. The catalyst was filtered on glass fiber paper and rinsed with EtOAc (100 mL). The filtrate was concentrated in vacuo to a yellow solid and taken up in EtOAc (150 mL). To the resultant solution was added 10% Pd/C (0.5 g). The mixture was further hydrogenated at 55 psi overnight. The catalyst was filtered off on glass fiber paper and rinsed with EtOAc (75 mL). The filtrate was concentrated in vacuo to give 13.0 g of 49b as an off-white solid (98%). 1H NMR (300 MHz, CDCl3): δ 7.99 (s, 1H), 7.32-7.23 (m, 1H), 7.10 (d, 1H), 6.67-6.55 (m, 3H), 6.43-6.35 (m, 2H), 4.65 (s, 2H), 3.96 (t, 2H), 3.83 (s, 3H), 3.83 (bs, 2H), 1.83 (nonet, 1H), 1.67 (qt, 2H), 0.96 (d, 6H) ppm. HPLC analysis (10:10:80 H2O:A1:MeOH) showed a purity of 98% with a retention time of 4.8 min.

Workup

  1. customwas hydrogenated on a Parr shaker at 58 psi overnight
  2. additionmixed with the catalyst
  3. filtrationThe catalyst was filtered on glass fiber paper
  4. washrinsed with EtOAc (100 mL)
  5. concentrationThe filtrate was concentrated in vacuo to a yellow solid
  6. additionTo the resultant solution was added 10% Pd/C (0.5 g)
  7. customwas further hydrogenated at 55 psi overnight
  8. filtrationThe catalyst was filtered off on glass fiber paper
  9. washrinsed with EtOAc (75 mL)
  10. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-283c2639b29245ec87c0b0ec9f8ea3f1
Source dataset
uspto-grants-2014_10
Patent number
US08859780B2

Reaction notes

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