4-Methylmorpholine → Z-Sta-Ala-OC(CH3)3

HRID 1982320Notes

Reaction equation

HRID 1982320 reaction equation
[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C@H:7]([CH2:9][C:10]([OH:12])=O)[OH:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[NH2:23][C@H:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH3:25].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.O>[NH:1]([C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])[C@H:2]([C@H:7]([CH2:9][C:10]([NH:23][C@H:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH3:25])=[O:12])[OH:8])[CH2:3][CH:4]([CH3:5])[CH3:6]

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 89016L-Alanine 1,1-dimethylethyl esterHCID 14560231Z-Sta-OH

Product 1

HCID 131714736Z-Sta-Ala-OC(CH3)3

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

371 mg of Z-Sta-OH (cf. stage 1.12), 240 mg of H-Ala-OC(CH3)3 and 184 mg of HOBt×H2O are dissolved in 10 ml of DMF. After cooling the solution to 0°, 133 mg of N-methylmorpholine and 321 mg of DCCI are added. The whole is stirred for 1 hour at 0° and for 14 hours at 25°, then the DCH formed is filtered off and the filtrate is concentrated to dryness by evaporation. The residue is taken up in ethyl acetate and the solution is extracted with saturated sodium bicarbonate solution. The organic phases are dried, concentrated by evaporation and the residue is flash-chromatographed over 80 g of silica gel (grain size 0.04-0.063 mm) [eluant: methylene chloride/ether (4:1), fractions of approximately 25 ml]. Fractions 24-40 are combined, concentrated by evaporation, the residue is dissolved in a small amount of methylene chloride, and the solution is filtered and concentrated by evaporation once more. After drying the residue in a high vacuum, Z-Sta-Ala-OC(CH3)3 is obtained as a slightly yellowish oil; Rf (methylene chloride/diethyl ether [4:1])=0.10.

Workup

  1. temperatureAfter cooling the solution to 0°
  2. customthe DCH formed
  3. filtrationis filtered off
  4. concentrationthe filtrate is concentrated to dryness by evaporation
  5. extractionthe solution is extracted with saturated sodium bicarbonate solution
  6. customThe organic phases are dried
  7. concentrationconcentrated by evaporation
  8. customthe residue is flash-chromatographed over 80 g of silica gel (grain size 0.04-0.063 mm) [eluant: methylene chloride/ether (4:1), fractions of approximately 25 ml]
  9. concentrationconcentrated by evaporation
  10. dissolutionthe residue is dissolved in a small amount of methylene chloride
  11. filtrationthe solution is filtered
  12. concentrationconcentrated by evaporation once more
  13. customAfter drying the residue in a high vacuum

Sources & evidence

ORD record
ord-056932ce375f4aeca6c15f8c5ef44a5b
Source dataset
uspto-grants-1986_06
Patent number
US04595677

Reaction notes

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