Imidazole → HCID 70049356, compound

HRID 1030201Notes

Reaction equation

HRID 1030201 reaction equation
N1C=CN=C1.P(Cl)(Cl)(OC1C=CC=CC=1)=O.[CH2:17]([O:24][C:25]([NH:27][C@H:28]([C:33]([OH:35])=O)[CH2:29][CH:30]([CH3:32])[CH3:31])=[O:26])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[NH2:36][C@@H:37]([CH2:45][CH:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1)[C@H:38]([C:40]1[O:41][CH:42]=[CH:43][CH:44]=1)[OH:39]>ClCCl.O1CCCC1.CN(C)C=O>[CH2:17]([O:24][C:25]([NH:27][C@H:28]([C:33]([NH:36][C@@H:37]([CH2:45][CH:46]1[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]1)[C@H:38]([C:40]1[O:41][CH:42]=[CH:43][CH:44]=1)[OH:39])=[O:35])[CH2:29][CH:30]([CH3:31])[CH3:32])=[O:26])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

8

Reactant 4

HCID 795Imidazole2×HCID 13038Phosphorodichloridic acid, phenyl esterHCID 74840Leucine, N-carboxy-, N-benzyl ester, L-HCID 10933089HCID 10933089, compound

Product 1

HCID 70049356HCID 70049356, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 1.4 g of imidazole in 18 ml of dichloromethane is added 0.90 ml of phenyl dichlorophosphate in 6 ml of dichloromethane. The mixture is stirred for 20 minutes, cooled to 0° C. and a solution of 0.60 g of imidazole, 2.4 ml of N,N-dimethylformamide and 1.6 g of Nα -[(benzyloxy)carbonyl]-L-leucine in 6 ml of tetrahydrofuran added. The mixture is stirred at 0°C. for 40 minutes and then 1.30 g of (S)-2-amino-3-cyclohexyl-(R)-1-(2-furanyl)propan-1-ol added. The mixture is stirred at 0° C. to 25° C. (ice bath allowed to melt) overnight and the solvent removed. The residue is dissolved in 20 ml of ethyl acetate and washed with water, 2N citric acid, sodium bicarbonate solution and dried (MgSO4). The solution is filtered through a thin pad of hydrous magnesium silicate and the pad washed with several volumes of ethyl acetate. The filtrate is concentrated under vacuum to give 2.3 g of N-[N-(benzyloxy)carbonyl-L-leucyl]-(S)-2-amino-3-cyclohexyl-(R)-1-(2-furanyl)propan-1-ol as an oil. The preceding compound (1.85 g) and 1.0 g of ammonium formate in 24 ml of methanol under nitrogen is warmed on a steam bath and then the solution is chilled to 0° C. To the mixture (without stirring) is added (by pipette) 0.96 g of 10% palladium on carbon suspended in 5 ml of ethanol. The mixture is stirred at 0° C. for one hour, diatomaceous earth added and the mixture filtered. The filter pad is washed with methanol and the filtrate evaporated to dryness. The residue is partitioned between ammonium hydroxide and dichloromethane. The organic layer is separated, dried (MgSO4) and the solvent removed to give 1.24 g of a gum. Crystallization from 5 ml of diisopropyl ether gives 0.74 g of N-(L-leucyl)-(S)-2-amino-3-cyclohexyl-(R)-1-(2-furanyl)propan-1-ol as colorless crystals, mp 83°-84° C. [α]D26 -17°±1 (c, 1.031, CH3OH).

Workup

  1. stirringThe mixture is stirred at 0°C. for 40 minutes
  2. stirringThe mixture is stirred at 0° C. to 25° C. (ice bath allowed to melt) overnight
  3. customthe solvent removed
  4. dissolutionThe residue is dissolved in 20 ml of ethyl acetate
  5. washwashed with water, 2N citric acid, sodium bicarbonate solution
  6. dry with materialdried (MgSO4)
  7. filtrationThe solution is filtered through a thin pad of hydrous magnesium silicate
  8. washthe pad washed with several volumes of ethyl acetate
  9. concentrationThe filtrate is concentrated under vacuum

Sources & evidence

ORD record
ord-3a484410e54540aa8d7e9fedc230f3b1
Source dataset
uspto-grants-1992_04
Patent number
US05104869

Reaction notes

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