Hydrochloric Acid → HCID 69938689, compound

HRID 1058961Notes

Reaction equation

HRID 1058961 reaction equation
C1(N[CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)CCCCC1.[CH3:14][C:15]([CH3:33])([O:17][C:18](N(C)[C@H](C(O)=O)CC1C=CC=CC=1)=[O:19])[CH3:16].Cl.[CH3:35][N:36]1CC[O:39][CH2:38][CH2:37]1.Cl[C:43](OCC(C)C)=O.Cl.[CH3:51][O:52][C:53](=[O:56])[CH2:54][NH2:55]>O.ClCCl>[CH3:51][O:52][C:53](=[O:56])[CH2:54][NH:55][C:38](=[O:39])[C@@H:37]([NH:36][CH2:35][C:18]([O:17][C:15]([CH3:14])([CH3:16])[CH3:33])=[O:19])[CH2:43][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 122755Glycine methyl ester hydrochlorideHCID 16211321HCID 16211321, compound

Product 1

HCID 69938689HCID 69938689, compoundYield 100.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-[(1,1-Dimethylethoxy)carbonyl]-N-methyl-L-phenylalanine dicyclohexylamine salt (3.0 g, 6.5 mmol) was partitioned between dichloromethane (100 mL) and aqueous hydrochloric acid (0.1M, 100 mL). The layers were separated and the organic fraction was washed with aqueous hydrochloric acid (0.1M, 100 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was dissolved in dichloromethane (30 mL), cooled to 0° C. and N-methylmorpholine (0.72 mL, 0.66 g, 6.5 mmol) then isobutyl chloroformate (0.84 mL, 0.89 g, 6.5 mmol) were added. The mixture was stirred at 0° C. for 10 min., then N-methylmorpholine (0.72 mL, 0.66 g, 6.5 mmol) and glycine methyl ester hydrochloride (0.82 g, 6.5 mmol) were added. The mixture was stirred at 0° C. for 1 h., then at room temperature for 2 h. Water (100 mL) was added and the mixture was extracted with ethyl acetate (100 mL). The organic fraction was dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with hexane/EtOAc (50:50), to give the title compound as a colorless gum (2.28 g, 100%). 1H NMR (250 MHz, CDCl3) mixture of two amide rotamers; δ7.28-7.23 (5H, m), 6.66, 6.40 (total 1H, each br s), 5.01, 4.80 (total 1H, each m), 4.24-3.82 (2H, m), 3.75 (3H, s), 3.39 (1H, m), 2.94 (1H, m), 2.81, 2.76 (total 3H, each s), and 1.37, 1.27 (total 9H, each s). m/z (ES+) 351 (M+1).

Workup

  1. customThe layers were separated
  2. washthe organic fraction was washed with aqueous hydrochloric acid (0.1M, 100 mL)
  3. dry with materialdried (MgSO4)
  4. customthe solvent was evaporated under reduced pressure
  5. dissolutionThe residue was dissolved in dichloromethane (30 mL)
  6. stirringThe mixture was stirred at 0° C. for 1 h.
  7. waitat room temperature for 2 h
  8. extractionthe mixture was extracted with ethyl acetate (100 mL)
  9. dry with materialThe organic fraction was dried (MgSO4)
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was purified by flash column chromatography on silica gel
  12. washeluting with hexane/EtOAc (50:50)

Sources & evidence

ORD record
ord-9937ccc4e5b64d8bb925308ecc39cd54
Source dataset
uspto-grants-2003_02
Patent number
US06518273B1

Reaction notes

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