Methyl chloroformate → HCID 86587225, compound

HRID 2414693Notes

Reaction equation

HRID 2414693 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.[OH-].[Na+].Cl[C:36]([O:38][CH3:39])=[O:37].S([O-])(O)(=O)=O.[K+]>O1CCCC1>[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:36]([O:38][CH3:39])=[O:37])[C:29]([OH:31])=[O:30])=[O:25])[CH2:19]2)=[O:17])[CH2:12][CH2:13]1

Participants

6

Reactant 4

HCID 6586Methyl chloroformateHCID 14798Sodium HydroxideHCID 516920Potassium bisulfateHCID 11155260HCID 11155260, compound

Product 1

HCID 86587225HCID 86587225, compoundYield 71.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N-[(3R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-amino-β-alanine (250 mg) in a mixture of tetrahydrofuran (5 mL) and 1 N-aqueous sodium hydroxide solution (1.16 mL) was added dropwise methyl chloroformate (45 μL) at 4° C. After 15 minutes, the reaction mixture was acidified with 5% aqueous potassium hydrogensulfate solution and extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The organic layer was evaporated and the residue was treated with 4 N-hydrogen chloride in ethyl acetate. The resulting insoluble material was collected by filtration and dried. The dry material was dissolved in water. Thus obtained solution was neutralized with an aqueous saturated sodium hydrogencarbonate solution and lyophilized. The residue was purified by ODS column chromatography (Daisogel-120sp®) eluting with 2, 5 and 8% CH3CN/H2O and lyophilized to give N-[(3R)-1-{3-(4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-methoxycarbonylamino-β-alanine (162 mg, 71.4%) as an amorphous powder.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. customThe organic layer was evaporated
  5. additionthe residue was treated with 4 N-hydrogen chloride in ethyl acetate
  6. filtrationThe resulting insoluble material was collected by filtration
  7. customdried
  8. dissolutionThe dry material was dissolved in water
  9. customThe residue was purified by ODS column chromatography (Daisogel-120sp®)
  10. washeluting with 2, 5 and 8% CH3CN/H2O

Sources & evidence

ORD record
ord-f109e074cfd14251b1f407c4e0bdc1b4
Source dataset
uspto-grants-2004_11
Patent number
US06812235B2

Reaction notes

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