4-Methylmorpholine → HCID 131719432, compound

HRID 1683345Notes

Reaction equation

HRID 1683345 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[CH:32]=[CH:31][S:30][CH:29]=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[CH:32]=[CH:31][S:30][CH:29]=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 70049552N-Phthalimido-3-(3-thienyl)-L-alanineHCID 178418300HCID 178418300, compound

Product 1

HCID 131719432HCID 131719432, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-Methylmorpholine (1.89 ml., 18.12 mmol.) was added to a solution of 6-hydroxy-L-norleucine, methyl ester, hydrochloride (10.66 mmol.) in methylene chloride (41 ml.)/dimethylformamide (11 ml.) at room temperature under argon. The resulting mixture was cooled to 0° C. and N-phthalimido-3-(3-thienyl)-L-alanine (3.21 g., 10.66 mmol.), hydroxy-benzotriazole (1.48 g., 10.98 mmol.), and 1-ethyl-3-(3dimethylaminopropyl)carbodiimide (2.25 g., 11.73 mmol.) were added sequentially. After stirring at 0° C. for 30 minutes, the mixture was warmed to room temperature and stirred for 2 hours. The volatiles were evaporated and the residue was partitioned between ethyl acetate and water. The organic layer was washed successively with 0.5 N 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 4:1 ethyl acetate/hexane to give 3.8 g. of title compound as a white foam. TLC (ethyl acetate) Rf =0.56.

Workup

  1. temperaturethe mixture was warmed to room temperature
  2. stirringstirred for 2 hours
  3. customThe volatiles were evaporated
  4. customthe residue was partitioned between ethyl acetate and water
  5. washThe organic layer was washed successively with 0.5 N 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 4:1 ethyl acetate/hexane
  11. customto give 3.8 g

Sources & evidence

ORD record
ord-4c9defe7ece24b319cb199b42032325a
Source dataset
uspto-grants-1997_06
Patent number
US05637698

Reaction notes

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