4-Methylmorpholine → HCID 86587232, compound

HRID 2414697Notes

Reaction equation

HRID 2414697 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([NH:26][CH2:27][C@H:28]([NH2:32])[C:29]([OH:31])=[O:30])=[O:25])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=O)(C)(C)C.[SiH3]C[C:35](N)=[O:36].CN1CCOCC1.[CH:45]1([CH2:48][OH:49])[CH2:47][CH2:46]1.[Cl:50][C:51](Cl)([O:53]C(=O)OC(Cl)(Cl)Cl)Cl.OS([O-])(=O)=O.[K+]>C(#N)C.ClCCl.N1C=CC=CC=1>[Cl:50][C:51]([O:25][CH2:24][CH:20]1[CH2:21][CH2:22]1)=[O:53].[NH:8]1[CH2:9][CH2:10][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([NH:26][CH2:27][C@H:28]([NH:32][C:35]([O:49][CH2:48][CH:45]3[CH2:47][CH2:46]3)=[O:36])[C:29]([OH:31])=[O:30])=[O:25])[CH2:19]2)=[O:17])[CH2:12][CH2:13]1

Participants

11

Reactant 6

HCID 79724-MethylmorpholineHCID 75644CyclopropanemethanolHCID 94429TriphosgeneHCID 516920Potassium bisulfateHCID 11155260HCID 11155260, compoundHCID 123643341HCID 123643341, compound

Product 2

HCID 15917591Cyclopropylmethyl carbonochloridateHCID 86587232HCID 86587232, compoundYield 47.4%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of N-[(R)-1-{3-(1-tertbutoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-amino-β-alanine (207 mg, 0.45 mmol) in acetonitrile (7 mL) was added monosilylacetamide (0.8 g), then the mixture was stirred for 30 minutes at 45° C. After the mixture was allowed to cool to room temperature, N-methylmorpholine (50 mL, 0.45 mmol) and a solution of cyclopropylmethyl chloroformate (1 mmol) in dichloromethane (2 mL), which was prepared from cyclopropanemethanol, triphosgene and pyridine, was added successively via syringe. After stirring for 2 hours, the mixture was acidified with 20% aqueous KHSO4 solution, extracted with ethyl acetate and dried over sodium sulfate. After evaporation of the solvent, the residue was treated with 4N hydrochloric acid in ethyl acetate. The insoluble material was collected by filtration, dried and dissolved in water. The solution was neutralized with a saturated aqueous NaHCO3 solution, purified by an ODS column chromatography using Daisogel-120SP (10% CH3CN/water) and freeze-dried to give N-[(R)-1-{3-(4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-(cyclopropylmethyloxycarbonyl)amino-β-alanine (120 mg, 47.4%) as a white powder.

Workup

  1. temperatureto cool to room temperature
  2. additionwas added successively via syringe
  3. stirringAfter stirring for 2 hours
  4. extractionextracted with ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. customAfter evaporation of the solvent
  7. additionthe residue was treated with 4N hydrochloric acid in ethyl acetate
  8. filtrationThe insoluble material was collected by filtration
  9. customdried
  10. dissolutiondissolved in water
  11. custompurified by an ODS column chromatography
  12. customfreeze-dried

Sources & evidence

ORD record
ord-c7996411d7e04289a38aa412cb72e02b
Source dataset
uspto-grants-2004_11
Patent number
US06812235B2

Reaction notes

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