Triethylamine → HCID 178459631, compound

HRID 1608446Notes

Reaction equation

HRID 1608446 reaction equation
[F:1][C:2]1[CH:20]=[CH:19][CH:18]=[CH:17][C:3]=1[CH2:4][CH:5]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[F:16])[C:6]([OH:8])=O.Cl.Cl.[CH:23]([O:26][C:27](=[O:49])[CH:28]([OH:48])[C@@H:29]([NH:37][C:38](=[O:47])[C@H:39]([CH2:41][C:42]1[N:46]=[CH:45][NH:44][CH:43]=1)[NH2:40])[CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1)([CH3:25])[CH3:24].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C>CN(C)C=O>[CH:23]([O:26][C:27](=[O:49])[CH:28]([OH:48])[C@@H:29]([NH:37][C:38](=[O:47])[C@H:39]([CH2:41][C:42]1[N:46]=[CH:45][NH:44][CH:43]=1)[NH:40][C:6](=[O:8])[CH:5]([CH2:4][C:3]1[CH:17]=[CH:18][CH:19]=[CH:20][C:2]=1[F:1])[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[F:16])[CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1)([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 18957612HCID 18957612, compoundHCID 178459632HCID 178459632, compound

Product 1

HCID 178459631HCID 178459631, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

In 5 ml of N,N-dimethylformamide were dissolved 67 mg of bis(2-fluorobenzyl)acetic acid and 100 mg of (2RS, 3S)-3-[N-(L-histidyl)amino]-4-cyclohexyl-2-hydroxybutyric acid isopropyl ester dihydrochloride, and to the solution were successively added 0.06 ml of diphenylphosphoryl azide and 0.1 ml of triethylamine with stirring under ice-cooling. The mixture was still stirred for 16 hours, and the reaction mixture was evaporated under reduced pressure. To the residue was added an aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: chloroform/methanol=10/1) to 23 mg of (2RS, 3S)-3-{N-[bis(2-fluorobenzyl)acetyl]-L-histidyl}amino-4-cyclohexyl-2-hydroxybutyric acid isopropyl ester having an Rf2 value of 0.59 as a white powder.

Workup

  1. temperaturecooling
  2. stirringThe mixture was still stirred for 16 hours
  3. customthe reaction mixture was evaporated under reduced pressure
  4. additionTo the residue was added an aqueous sodium bicarbonate solution
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. customevaporated under reduced pressure
  9. customThe residue was purified by preparative silica gel thin layer chromatography (developing solvent: chloroform/methanol=10/1) to 23 mg of (2RS, 3S)-3-{N-[bis(2-fluorobenzyl)acetyl]-L-histidyl}amino-4-cyclohexyl-2-hydroxybutyric acid isopropyl ester having an Rf2 value of 0.59 as a white powder

Sources & evidence

ORD record
ord-847537deae3843a0a9a1483a5c5c6d61
Source dataset
uspto-grants-1989_09
Patent number
US04870183

Reaction notes

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