Ethyl orthoformate → HCID 67428261, compound

HRID 1667724Notes

Reaction equation

HRID 1667724 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[C:18]([NH:25][C:26]3[S:27][C:28]([C:38](=[O:40])[NH2:39])=[C:29]([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=4)[N:30]=3)[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:41](OCC)(OCC)OCC>C(O)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]3[N:22]=[CH:41][N:25]([C:26]4[S:27][C:28]([C:38](=[O:40])[NH2:39])=[C:29]([C:31]5[CH:36]=[CH:35][CH:34]=[C:33]([Cl:37])[CH:32]=5)[N:30]=4)[C:18]=3[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 31214Ethyl orthoformateHCID 86642829HCID 86642829, compound

Product 1

HCID 67428261HCID 67428261, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

The crude 4-{3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazole-2-ylamino]-4-nitro-phenoxymethyl}-piperidine-1-carboxylic acid tert-butyl ester (VII.23) 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 and then concentrated under reduced pressure. The residue was diluted with ethyl acetate and saturated aqueous sodium carbonate. 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 0.13 g of 4-{3-[5-carbamoyl-4-(3-chloro-phenyl)-thiazole-2-yl]-3H-benzoimidazol-5-yloxymethyl}-piperidine-1-carboxylic acid tert-butyl ester (I.23a).

Workup

  1. temperatureThe mixture was heated at 70 degrees for 2 hours
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with ethyl acetate and saturated aqueous sodium carbonate
  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-4b3a3dc62c7c41f09002314234ee719c
Source dataset
uspto-grants-2011_10
Patent number
US08044213B2

Reaction notes

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