Triethylamine → HCID 178485750, compound

HRID 1031756Notes

Reaction equation

HRID 1031756 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]([OH:18])=O)[CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)OCC.Cl.[CH3:33][N:34](C)[C:35](=[O:45])[C@H:36]([CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[NH2:37]>O1CCCC1.CN(C)C=O>[CH3:33][NH:34][C:35](=[O:45])[C@H:36]([CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[NH:37][C:16]([C@H:13]1[CH2:12][CH2:11][C@H:10]([CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:15][CH2:14]1)=[O:18]

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 10928Ethyl chloroformateHCID 12653778(2S)-2-Amino-N,N-dimethyl-3-phenylpropanamide hydrochlorideHCID 178453624HCID 178453624, compound

Product 1

HCID 178485750HCID 178485750, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To the compounds (I) (19.15 g) was added dry 1,4-dioxane (50 ml) and 4N hydrogen chloride/1,4-dioxane solution (250 ml), and the mixture was stirred under room temperature for 2 hours. The solvent was removed under a reduced pressure and toluene was added and reevaporated to give L-phenylalanine 4-carbamoylanilide hydrochloride (II) quantitatively as a white powder. On the other hand, trans-4-(t-butoxycarbonylaminomethyl)cyclohexylcarboxylic acid (13.36 g) was dissolved in dry tetrahydrofuran (500 ml), and triethylamine (7.80 ml) was added under ice-cooling, followed by stirring at the same temperature for 10 minutes. Subsequently, a solution of ethyl chlorocarbonate (5.64 g) in dry tetrahydrofuran (50 ml) was added dropwise under ice-cooling for 3 minutes, and the mixture was again stirred at the same temperature for 20 minutes. The above mixture was added to the suspension of the hydrochloride (II) previously obtained and triethylamine (8.53 ml) in N,N-dimethylformamide (150 ml) under ice-cooling, followed by stirring at the same temperature for 2 hours, and under room temperature for 6 hours. Ice-water (1.4 liter) was added and the insolubles were collected by filtration, thoroughly washed with water, and further washed with 10% aqueous citric acid, water 5% aqueous sodium hydrogen carbonate, followed by washing with water at 40° to 50° C., and drying, to give N-[4-trans-(t-butoxycarbonylaminomethyl)cyclohexylcarbonyl]-L-phenylalanine 4-carbamoylanilide (III) (24.63 g). The structure was confirmed by NMR.

Workup

  1. temperaturecooling
  2. temperaturecooling for 3 minutes
  3. stirringthe mixture was again stirred at the same temperature for 20 minutes
  4. custompreviously obtained
  5. stirringby stirring at the same temperature for 2 hours
  6. waitunder room temperature for 6 hours
  7. filtrationthe insolubles were collected by filtration
  8. washthoroughly washed with water
  9. washfurther washed with 10% aqueous citric acid, water 5% aqueous sodium hydrogen carbonate
  10. washby washing with water at 40° to 50° C.
  11. customdrying

Sources & evidence

ORD record
ord-a755bcc8a388454da3f63393f55da0be
Source dataset
uspto-grants-1990_09
Patent number
US04954512

Reaction notes

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