4-Methylmorpholine → HCID 178501402, compound

HRID 1607409Notes

Reaction equation

HRID 1607409 reaction equation
[C:1]1([CH2:11][CH:12]([CH2:16][CH2:17][CH2:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:13](O)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C1C(=O)N(OC(ON2C(=O)CCC2=O)=O)C(=O)C1.Cl.Cl.[CH3:46][O:47][C:48](=[O:57])[C@H:49]([CH2:51][C:52]1[N:56]=[CH:55][NH:54][CH:53]=1)[NH2:50].CN1CCOCC1>C(#N)C.C(Cl)(Cl)Cl.CN(C)C=O.C(N(CC)CC)C>[CH3:46][O:47][C:48](=[O:57])[C@H:49]([CH2:51][C:52]1[N:56]=[CH:55][NH:54][CH:53]=1)[NH:50][C:13](=[O:14])[CH:12]([CH2:11][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

9

Reactant 4

HCID 79724-MethylmorpholineHCID 676246Di(succinimido) carbonateHCID 137270912-(1-Naphthylmethyl)-6-phenylhexanoic acidHCID 178419105HCID 178419105, compound

Product 1

HCID 178501402HCID 178501402, compoundYield 63.4%

Reagents, catalysts & solvents 4

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 3.32 g of 2-(1-naphthylmethyl)-6-phenylhexanoic acid in 50 ml of dry acetonitrile were added 2.70 g of N,N'-disuccinimidylcarbonate and 2.0 ml of triethylamine with stirring at room temperature, and the mixture was stirred for 1 hour. The reaction mixture was added dropwise to a mixture of 2.42 g of L-histidine methyl ester dihydrochloride, 6 ml of N-methylmorpholine, 120 ml of dry N,N-dimethylformamide and 300 ml of dry chloroform, and the resulting mixture was stirred for 24 hours at 50° C. The reaction mixture was concentrated under reduced pressure and a 5% aqueous sodium bicarbonate solution was added to the residue and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography (eluent: chloroform/methanol=30/1 by volume) to obtain 3.06 g of N-[2-(1-naphthylmethyl)-6-phenylhexanoyl]-L-histidine methyl ester as a white powder.

Workup

  1. stirringthe mixture was stirred for 1 hour
  2. stirringthe resulting mixture was stirred for 24 hours at 50° C
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additiona 5% aqueous sodium bicarbonate solution was added to the residue
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe organic layer was washed with a saturated sodium chloride aqueous solution
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash column chromatography (eluent: chloroform/methanol=30/1 by volume)

Sources & evidence

ORD record
ord-172b4a3776a64954b726d0d3da7ff8bc
Source dataset
uspto-grants-1989_09
Patent number
US04863904

Reaction notes

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