Tetrahydrofuran → 1,1-Dimethylethyl 4-{6-[(1-methylethyl)oxy]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-piperidinecarboxylate

HRID 2064078Notes

Reaction equation

HRID 2064078 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]([CH3:11])[CH3:10])=[CH:4][C:3]=1[NH:12][CH:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]1.[O:26]1CCC[CH2:27]1>>[CH3:11][CH:9]([O:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:27](=[O:26])[N:12]([CH:13]3[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:23])([CH3:25])[CH3:24])=[O:20])[CH2:15][CH2:14]3)[C:3]=2[CH:4]=1)[CH3:10]

Participants

3

Reactant 2

HCID 8028TetrahydrofuranHCID 574239171,1-Dimethylethyl 4-({2-amino-5-[(1-methylethyl)oxy]phenyl}amino)-1-piperidinecarboxylate

Product 1

HCID 574239181,1-Dimethylethyl 4-{6-[(1-methylethyl)oxy]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl}-1-piperidinecarboxylateYield 69%

Conditions

Temperature
50 °C

Procedure

A solution of 1,1-dimethylethyl 4-({2-amino-5-[(1-methylethyl)oxy]phenyl}amino)-1-piperidinecarboxylate (D48, 470 mg, 1.34 mmol) in tetrahydrofuran (5 ml) was treated with N,N′-carbonyldiimidazole (322 mg, 2.01 mmol) and heated at 50° C. for 17 hrs. The mixture was concentrated under vacuum and the residue treated with Na2CO3 solution (10 ml) and extracted with ethyl acetate (2×20 ml). The combined extract was dried (MgSO4), concentrated under vacuum and the residue purified by chromatography on silica gel eluting with 5-60% ethyl acetate/60-80 petrol ether to afford the title compound as a dark orange oil (351 mg, 69%). M+−H=374.3.

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. additionthe residue treated with Na2CO3 solution (10 ml)
  3. extractionextracted with ethyl acetate (2×20 ml)
  4. extractionThe combined extract
  5. dry with materialwas dried (MgSO4)
  6. concentrationconcentrated under vacuum
  7. customthe residue purified by chromatography on silica gel eluting with 5-60% ethyl acetate/60-80 petrol ether

Sources & evidence

ORD record
ord-43ba41464eab4d638226b11d5ff94309
Source dataset
uspto-grants-2012_10
Patent number
US08288413B2

Reaction notes

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