Ethyl orthoformate → HCID 67426381, compound

HRID 1667719Notes

Reaction equation

HRID 1667719 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-])=O)=[C:17]([NH:24][C:25]3[S:26][C:27]([C:37](=[O:39])[NH2:38])=[C:28]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=4)[N:29]=3)[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:40](OCC)(OCC)OCC>C(O)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]3[N:21]=[CH:40][N:24]([C:25]4[S:26][C:27]([C:37](=[O:39])[NH2:38])=[C:28]([C:30]5[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[CH:31]=5)[N:29]=4)[C:17]=3[CH:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 86642828HCID 86642828, compound

Product 1

HCID 67426381HCID 67426381, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

The crude 4-{3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazole-2-ylamino]-4-nitro-phenoxy}-piperidine-1-carboxylic acid tert-butyl ester (VII.21) was dissolved in 4 mL of acetic acid and 0.14 mL (0.84 mmole) of triethyl orthoformate. The mixture was heated at 70 degrees for 2 hours. The reaction mixture was concentrated under reduced pressure. The residue was diluted with ethyl acetate and saturated aqueous sodium carbonate solution. The organic phase was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with ethyl acetate-dichloromethane (gradient 50:50-100:0) to give 0.10 g of 4-{3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazole-2-yl]-3H-benzoimidazol-5-yloxy}-piperidine-1-carboxylic acid tert-butyl ester (I.21a).

Workup

  1. temperatureThe mixture was heated at 70 degrees for 2 hours
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionThe residue was diluted with ethyl acetate and saturated aqueous sodium carbonate solution
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with ethyl acetate-dichloromethane (gradient 50:50-100:0)

Sources & evidence

ORD record
ord-6a969474219049c5b9f04661e3c695dd
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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