4-Methylmorpholine → N-[N-Phthalimido-3-(2-thienyl)-L-alanyl]-6-hydroxy-L-norleucine, methy ester

HRID 260217Notes

Reaction equation

HRID 260217 reaction equation
CN1CCOCC1.Cl.[OH:9][CH2:10][CH2:11][CH2:12][CH2:13][C@@H:14]([C:16]([O:18][CH3:19])=[O:17])[NH2:15].[C:20]1(=[O:41])[N:24]([NH:25][C@H:26]([C:33](O)=[O:34])[CH2:27][C:28]2[S:29][CH:30]=[CH:31][CH:32]=2)[C:23](=[O:36])[C:22]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:21]12.OC1C2N=NNC=2C=CC=1.C(N=C=NCCCN(C)C)C>C(Cl)Cl.CN(C)C=O>[C:23]1(=[O:36])[N:24]([NH:25][C@H:26]([C:33]([NH:15][C@H:14]([C:16]([O:18][CH3:19])=[O:17])[CH2:13][CH2:12][CH2:11][CH2:10][OH:9])=[O:34])[CH2:27][C:28]2[S:29][CH:30]=[CH:31][CH:32]=2)[C:20](=[O:41])[C:21]2=[CH:40][CH:39]=[CH:38][CH:37]=[C:22]12

Participants

8

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 11680005methyl (2S)-2-amino-6-hydroxyhexanoate hydrochlorideHCID 70051103HCID 70051103, compoundHCID 178418300HCID 178418300, compound

Product 1

HCID 131719431N-[N-Phthalimido-3-(2-thienyl)-L-alanyl]-6-hydroxy-L-norleucine, methy ester

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-Methylmorpholine (1.51 ml., 14.5 mmol.) was added to a solution of 6-hydroxy-L-norleucine, methyl ester, hydrochloride (8.53 mmol.) in methylene chloride (34 ml)/dimethylformamide (9 ml.) at room temperature under argon. The resulting mixture was cooled to 0° C. and N-phthalimido-3-(2-thienyl)-L-alanine (2.57 g., 8.54 mmol.), hydroxybenzotriazole (1.19 g., 8.80 mmol.) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (1.80 g., 9.4 mmol.) were added sequentially. After stirring at 0° C. for 30 minutes, the mixture was warmed to room temperature and stirred for 1.5 hours. The volatiles were evaporated and the residue was partitioned between ethyl acetate and water. The organic layer was washed successively with 0.5N hydrochloric acid, water, saturated sodium bicarbonate, and brine, and the organic layer was dried (sodium sulfate), filtered, and concentrated. The residue was flash chromatographed (Merck silica gel) eluting with 2:1 ethyl acetate/hexane to give 3.13 g. of title compound as a white foam. TLC (5% acetic acid in ethyl acetate) Rf =0.68.

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. stirringstirred for 1.5 hours
  3. customThe volatiles were evaporated
  4. customthe residue was partitioned between ethyl acetate and water
  5. washThe organic layer was washed successively with 0.5N hydrochloric acid, water, saturated sodium bicarbonate, and brine
  6. dry with materialthe organic layer was dried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed (Merck silica gel)
  10. washeluting with 2:1 ethyl acetate/hexane
  11. customto give 3.13 g

Sources & evidence

ORD record
ord-58fea3bc33c7485cb260f366ba6b3888
Source dataset
uspto-grants-1996_06
Patent number
US05525723

Reaction notes

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