Sodium Hydroxide → 5-Methoxy-2-[2-(2,4,6-trimethyl-phenyl)-acetyl]-[1,2,5]triazepane-1-carboxylic acid ethyl ester

HRID 924601Notes

Reaction equation

HRID 924601 reaction equation
[CH2:1]([O:3][C:4]([NH:6][NH:7][C:8](=[O:19])[CH2:9][C:10]1[C:15]([CH3:16])=[CH:14][C:13]([CH3:17])=[CH:12][C:11]=1[CH3:18])=[O:5])[CH3:2].[OH-].[Na+].CS(O[CH2:27][CH2:28][N:29]([O:37][CH3:38])[CH2:30][CH2:31]OS(C)(=O)=O)(=O)=O>C1(C)C=CC=CC=1.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([O:3][C:4]([N:6]1[CH2:31][CH2:30][N:29]([O:37][CH3:38])[CH2:28][CH2:27][N:7]1[C:8](=[O:19])[CH2:9][C:10]1[C:11]([CH3:18])=[CH:12][C:13]([CH3:17])=[CH:14][C:15]=1[CH3:16])=[O:5])[CH3:2]

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 71145194N'-[2-(2,4,6-Trimethyl-phenyl)-acetyl]-hydrazinecarboxylic acid ethyl esterHCID 86719909Methanesulfonic acid 2-[(2-methanesulfonyloxy-ethyl)-methoxy-amino]-ethyl ester

Product 1

HCID 867199175-Methoxy-2-[2-(2,4,6-trimethyl-phenyl)-acetyl]-[1,2,5]triazepane-1-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
65 °C

Procedure

To a vigorously stirred suspension of N′-[2-(2,4,6-trimethyl-phenyl)-acetyl]-hydrazinecarboxylic acid ethyl ester (4.22 g, 15.96 mmol) in toluene (80 ml) was added aqueous sodium hydroxide (12 ml, 30% NaOH w/w in water) and tetra-butyl ammonium bromide (160 mg, 0.48 mmol) at room temperature, followed by methanesulfonic acid 2-[(2-methanesulfonyloxy-ethyl)-methoxy-amino]-ethyl ester (4.66 g, 16.00 mmol) dropwise over 15 minutes at 65° C. The reaction mixture was heated at 65° C. for 6.5 hours. After cooling, the layers were separated, the organic phase evaporated, the residue dissolved in ethyl acetate, washed with water, dried over sodium sulfate and concentrated. The residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate/dichloromethane 5:4:1). Yield: 2.6 g of 5-methoxy-2-[2-(2,4,6-trimethyl-phenyl)-acetyl]-[1,2,5]triazepane-1-carboxylic acid ethyl ester (compound P3.1) as a colorless oil.

Workup

  1. temperatureAfter cooling
  2. customthe layers were separated
  3. customthe organic phase evaporated
  4. dissolutionthe residue dissolved in ethyl acetate
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by chromatography on silica gel (cyclohexane/ethyl acetate/dichloromethane 5:4:1)

Sources & evidence

ORD record
ord-2990e317e520401c94519301f4422b41
Source dataset
uspto-grants-2016_03
Patent number
US09282743B2

Reaction notes

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