2-(3-Ethoxyphenoxy)-N-[4-hydroxy-2-(isobutylamino)phenyl]acetamide → 2-[(3-Ethoxyphenoxy)methyl]-1-isobutylbenzimidazol-6-ol

HRID 537314Notes

Reaction equation

HRID 537314 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:24]=[CH:25][CH:26]=1)[O:7][CH2:8][C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][C:13]=1[NH:19][CH2:20][CH:21]([CH3:23])[CH3:22])=O)[CH3:2]>CC(O)=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:24]=[CH:25][CH:26]=1)[O:7][CH2:8][C:9]1[N:19]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:13]2[CH:14]=[C:15]([OH:18])[CH:16]=[CH:17][C:12]=2[N:11]=1)[CH3:2]

Participants

3

Reactant 1

HCID 866892922-(3-Ethoxyphenoxy)-N-[4-hydroxy-2-(isobutylamino)phenyl]acetamide

Product 1

HCID 866892932-[(3-Ethoxyphenoxy)methyl]-1-isobutylbenzimidazol-6-olYield 87.4%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A 250 mL flask fitted with a stir-bar and condenser was charged with amine 65b (10.0 g, 27.9 mmol) and AcOH (100 mL). The resultant solution was heated in a 100° C. bath for 1 hr, then concentrated in vacuo to a brown oil. The oil was taken up in EtOAc (200 mL) and washed with saturated NaHCO3 (2×100 mL) and brine (100 mL). Isopropanol (50 mL) and CH2Cl2 (50 mL) were added to break the emulsion. The organic solution was filtered through phase separation paper and concentrated in vacuo to a red-tan solid. The solid was triturated with hexanes:EtOAc 9:1 (50 mL), filtered, pressed with rubber dam, and rinsed with hexanes:EtOAc 9:1 (2×20 mL). The solid was dried to give 8.3 g of 66b as a tan solid (87%). 1H NMR (300 MHz, CDCl3): δ 8.84 (s, 1H), 7.37 (d, 1H), 7.02 (t, 1H), 6.70 (dd, 1H), 6.65 (d, 1H), 6.48 (dd, 1H), 6.44 (t, 1H), 6.37 (dd, 1H), 5.10 (s, 2H), 3.86 (t, 2H), 3.81 (d, 2H), 2.15 (nonet, 1H), 1.23 (t, 3H), 0.78 (d, 6H) ppm. HPLC analysis (0:10:90 H2O:A1:MeOH) showed a purity of 99% with a retention time of 3.5 min.

Workup

  1. customA 250 mL flask fitted with a stir-bar and condenser
  2. concentrationconcentrated in vacuo to a brown oil
  3. washwashed with saturated NaHCO3 (2×100 mL) and brine (100 mL)
  4. additionIsopropanol (50 mL) and CH2Cl2 (50 mL) were added
  5. filtrationThe organic solution was filtered through phase separation paper
  6. concentrationconcentrated in vacuo to a red-tan solid
  7. customThe solid was triturated with hexanes:EtOAc 9:1 (50 mL)
  8. filtrationfiltered
  9. washrinsed with hexanes:EtOAc 9:1 (2×20 mL)
  10. customThe solid was dried

Sources & evidence

ORD record
ord-2692b1236ffc4e5d83f908e0d8042ce6
Source dataset
uspto-grants-2014_10
Patent number
US08859780B2

Reaction notes

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