Dimethylformamide → N-(4-(1-benzyloxycarbonylamino-1-methylethyl)phenylmethyl)acetamide

HRID 1282120Notes

Reaction equation

HRID 1282120 reaction equation
[C:1]([NH:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([CH3:17])([CH3:16])C(O)=O)=[CH:8][CH:7]=1)(=[O:3])[CH3:2].C[N:19](C)[CH:20]=[O:21].C(Cl)(=O)[O:24][CH2:25][CH3:26].[N-]=[N+]=[N-].[Na+]>CC(C)=O.O.C(N(CC)CC)C>[CH2:25]([O:24][C:20]([NH:19][C:12]([C:9]1[CH:8]=[CH:7][C:6]([CH2:5][NH:4][C:1](=[O:3])[CH3:2])=[CH:11][CH:10]=1)([CH3:16])[CH3:17])=[O:21])[C:26]1[CH:10]=[CH:11][CH:6]=[CH:7][CH:8]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10928Ethyl chloroformateHCID 33557Sodium AzideHCID 184231082-(4-Acetamidomethylphenyl)-2-methylpropionic acid

Product 1

HCID 18423140N-(4-(1-benzyloxycarbonylamino-1-methylethyl)phenylmethyl)acetamide

Reagents, catalysts & solvents 3

HCID 180AcetoneSolvent2×HCID 962WaterSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(4-acetylaminomethylphenyl)-2-methylpropionic acid (14 g) in a mixed solvent of acetone (40 ml) and dimethylformamide (30 ml) was added triethylamine (8.75 ml) under ice-cooling and a solution of ethyl chlorocarbonate (6.76 g) in acetone (20 ml) was added dropwise over 10 min. The mixture was stirred at 0° C. for 15 min. To this solution was added dropwise a solution of sodium azide (4.26 g) in water (28 ml) under ice-cooling over 10 min, and the mixture was stirred for 30 min. The reaction mixture was poured into ice water (500 ml) and extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the obtained oil was dissolved in toluene (100 ml) and heated at 80° C. for 2 hr. To this solution was added benzyl alcohol (6.77 ml) and the mixture was stirred at 80° C. for 42 hr. To the reaction mixture was added isopropyl alcohol to allow crystallization to give the title compound (14.62 g) as white crystals, m.p.=132-135° C.

Workup

  1. temperaturecooling
  2. temperaturecooling over 10 min
  3. stirringthe mixture was stirred for 30 min
  4. extractionextracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated
  8. dissolutionthe obtained oil was dissolved in toluene (100 ml)
  9. temperatureheated at 80° C. for 2 hr
  10. additionTo this solution was added benzyl alcohol (6.77 ml)
  11. stirringthe mixture was stirred at 80° C. for 42 hr
  12. additionTo the reaction mixture was added isopropyl alcohol
  13. customcrystallization

Sources & evidence

ORD record
ord-b6216a88cade4ca4b63822c00c627493
Source dataset
uspto-grants-2002_09
Patent number
US06455528B1

Reaction notes

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