Hydrochloric Acid → Ethyl (+)-2-[4-[((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy]phenyl]-3-(7-amidino-2-naphthyl)propionate Dihydrochloride

HRID 54002

Reaction equation

HRID 54002 reaction equation
[ClH:1].Cl.[C:3]([C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][C:12]([CH2:16][CH:17]([C:23]3[CH:28]=[CH:27][C:26]([O:29][C@H:30]4[CH2:34][CH2:33][NH:32][CH2:31]4)=[CH:25][CH:24]=3)[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:13]2)=[CH:8][CH:7]=1)(=[NH:5])[NH2:4].Cl.[C:36](=[NH:41])(OCC)[CH3:37].C(N(CC)CC)C.Cl>C(O)C>[ClH:1].[ClH:1].[C:36]([N:32]1[CH2:33][CH2:34][C@H:30]([O:29][C:26]2[CH:27]=[CH:28][C:23]([CH:17]([CH2:16][C:12]3[CH:11]=[CH:10][C:9]4[C:14](=[CH:15][C:6]([C:3](=[NH:4])[NH2:5])=[CH:7][CH:8]=4)[CH:13]=3)[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:24][CH:25]=2)[CH2:31]1)(=[NH:41])[CH3:37]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 2724290Ethanimidic acid, ethyl ester, hydrochloride (1:1)HCID 70075336ethyl (+)-3-(7-amidino-2-naphthyl)-2-[4-[((3S)-3-pyrrolidinyl)oxy]phenyl]propionate dihydrochloride

Product 1

HCID 86750015Ethyl (+)-2-[4-[((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy]phenyl]-3-(7-amidino-2-naphthyl)propionate DihydrochlorideYield 193.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In 1,000 ml of ethanol was dissolved 105.3 g of ethyl (+)-3-(7-amidino-2-naphthyl)-2-[4-[((3S)-3-pyrrolidinyl)oxy]phenyl]propionate dihydrochloride. With stirring at room temperature, the thus prepared solution was mixed with 51.5 g of ethyl acetimidate hydrochloride. With ice cooling and stirring, 89 ml of triethylamine was added dropwise to the above solution while keeping the inner temperature at 3° to 5° C., and the stirring was continued for 2.5 hours while keeping the temperature at 5° C. or below. After distilling off the solvent under a reduced pressure at a low temperature, the resulting reaction solution was adjusted to pH 4-5 with dilute hydrochloric acid, followed by further distillation under a reduced pressure to remove the solvent. The resulting residue was purified by subjecting it to column chromatography using a column packed with a highly porous polymer type synthetic adsorbent (styrene-divinylbenzene polymer: Diaion HP-20) and using a water/acetonitrile mixture as an elution solvent. Thereafter, thus eluted fractions of interest were pooled, mixed with a small amount of dilute hydrochloric acid, and then concentrated to dryness. In this way, 110.1 g of the title compound was obtained in the form of a colorless solid.

Workup

  1. stirringWith ice cooling and stirring
  2. customat 3° to 5° C.
  3. customat 5° C. or below
  4. distillationAfter distilling off the solvent under a reduced pressure at a low temperature
  5. customthe resulting reaction solution
  6. distillationfollowed by further distillation under a reduced pressure
  7. customto remove the solvent
  8. customThe resulting residue was purified
  9. additionmixed with a small amount of dilute hydrochloric acid
  10. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-9f80b86c5f5a42c1abe63d6b1c022132
Source dataset
uspto-grants-1997_04
Patent number
US05620991

Linked notes

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