N-[2-(Isobutylamino)-4-(3-methylbutoxy)phenyl]-2-(3-methoxyphenoxy)acetamide → 1-Isobutyl-2-(3-methoxy-phenoxymethyl)-6-(3-methyl-butoxy)-1H-benzimidazole

HRID 537296Notes

Reaction equation

HRID 537296 reaction equation
[CH2:1]([NH:5][C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH:9]=[CH:8][C:7]=1[NH:18][C:19](=O)[CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=1)[CH:2]([CH3:4])[CH3:3]>CC(O)=O>[CH2:1]([N:5]1[C:6]2[CH:11]=[C:10]([O:12][CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH:9]=[CH:8][C:7]=2[N:18]=[C:19]1[CH2:20][O:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH3:29])[CH:23]=1)[CH:2]([CH3:4])[CH3:3]

Participants

3

Reactant 1

HCID 86689285N-[2-(Isobutylamino)-4-(3-methylbutoxy)phenyl]-2-(3-methoxyphenoxy)acetamide

Product 1

HCID 716208311-Isobutyl-2-(3-methoxy-phenoxymethyl)-6-(3-methyl-butoxy)-1H-benzimidazoleYield 87%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A 250 mL flask fitted with a stir-bar, condenser, and an Ar inlet was charged with amine 50b (10.7 g, 25.8 mmol) and AcOH (110 mL). The resultant solution was heated in a 100° C. bath for 3 hr. The mixture was cooled and concentrated in vacuo to an orange solid. The solid was partitioned with EtOAc (150 mL) and saturated NaHCO3 (100 mL). The organic phase was then washed with brine (100 mL), filtered through phase separation paper, and concentrated in vacuo to 10.6 g of a red oil. The oil was chromatographed on silica gel eluting the product with 10-15% EtOAc in hexanes. The product fractions were concentrated in vacuo to give 8.9 g of Compound #2 as an orange oil, which slowly crystallized (87%). 1H NMR (300 MHz, CDCl3): δ 7.66 (d, 1H), 7.22 (t, 1H), 7.27 (t, 1H), 6.93 (dd, 1H), 6.82 (d, 1H), 6.69 (dd, 1H), 6.63 (t, 1H), 6.57 (dd, 1H), 5.32 (s, 2H), 4.06 (t, 2H), 4.04 (d, 2H), 3.81 (s, 3H), 2.36 (nonet, 1H), 1.90 (nonet, 1H), 1.74 (qt, 2H), 1.00 (d, 6H), 0.97 (d, 6H) ppm. HPLC analysis (0:10:90 H2O:A1:MeOH) showed a purity of 98% with a retention time of 5.8 min.

Workup

  1. customA 250 mL flask fitted with a stir-bar, condenser
  2. temperatureThe mixture was cooled
  3. concentrationconcentrated in vacuo to an orange solid
  4. customThe solid was partitioned with EtOAc (150 mL) and saturated NaHCO3 (100 mL)
  5. washThe organic phase was then washed with brine (100 mL)
  6. filtrationfiltered through phase separation paper
  7. concentrationconcentrated in vacuo to 10.6 g of a red oil
  8. customThe oil was chromatographed on silica gel eluting the product with 10-15% EtOAc in hexanes
  9. concentrationThe product fractions were concentrated in vacuo

Sources & evidence

ORD record
ord-5912c4fdd4d24db798992c3f37368cef
Source dataset
uspto-grants-2014_10
Patent number
US08859780B2

Reaction notes

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