Hydroxylamine → HCID 53743075, compound

HRID 1974636Notes

Reaction equation

HRID 1974636 reaction equation
[C:1]([O:5][C:6]([CH:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13]1[C:14]([F:31])=[CH:15][C:16]2[N:20]=[C:19]([CH2:21][C:22](OCC)=[O:23])[N:18]([CH:27]3[CH2:29][CH2:28]3)[C:17]=2[CH:30]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:32][OH:33].C[O-].[Na+].N12CCCN=C1CCCCC2.[CH2:48](Br)[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C(O)C.O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[C@@H:8]1[CH2:12][CH2:11][CH2:10][N:9]1[C:13]1[C:14]([F:31])=[CH:15][C:16]2[N:20]=[C:19]([CH2:21][C:22](=[O:23])[NH:32][O:33][CH2:48][C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[N:18]([CH:27]3[CH2:29][CH2:28]3)[C:17]=2[CH:30]=1)([CH3:3])([CH3:2])[CH3:4]

Participants

9

Reactant 5

HCID 787HydroxylamineHCID 7498Benzyl BromideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 10942334Sodium MethoxideHCID 19101716HCID 19101716, compound

Product 1

HCID 53743075HCID 53743075, compoundYield 46.8%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ethyl rac-6-[2-(tert-butoxycarbonyl)-1-pyrrolidinyl]-1-cyclopropyl-5-fluoro-2-benzimidazoleacetate (1.647 g, 3.82 mmol) in ethanol (15 ml) is treated with a 1N ethanolic solution of hydroxylamine (9.54 ml, 9.54 mmol) and with a 1N ethanolic sodium methylate solution (1.91 ml, 1.91 mmol). After one hour the solvent is distilled off and the residue is dissolved in water. The pH is adjusted to 5.5 with 1N hydrochloric acid. This solution is extracted with ethyl acetate and the organic phase is washed with water, dried (magnesium sulfate) and concentrated. The residue is recrystallized from ethyl acetate. The crystals obtained are dissolved in tetrahydrofuran (30 ml) and treated with 1,8-diazabicyclo[5.4.0]undec-7-ene (377 mg, 2.5 mmol) and benzyl bromide (462 mg, 2.7 mmol). After 4 hours the reaction solution is diluted with ethyl acetate (150 ml) and washed with water (100 ml) and subsequently with 10 percent sodium chloride solution (100 ml). The organic phase is dried (magnesium sulfate) and concentrated. The residue is recrystallized from ether/n-hexane. There are obtained 643 mg (33%) of 1-[2-[[(benzyloxy)carbamoyl]methyl]-1-cyclopropyl-5-fluoro-6-benzimidazolyl]-L-proline tert-butyl ester.

Workup

  1. distillationAfter one hour the solvent is distilled off
  2. dissolutionthe residue is dissolved in water
  3. extractionThis solution is extracted with ethyl acetate
  4. washthe organic phase is washed with water
  5. dry with materialdried (magnesium sulfate)
  6. concentrationconcentrated
  7. customThe residue is recrystallized from ethyl acetate
  8. customThe crystals obtained
  9. washwashed with water (100 ml) and subsequently with 10 percent sodium chloride solution (100 ml)
  10. dry with materialThe organic phase is dried (magnesium sulfate)
  11. concentrationconcentrated
  12. customThe residue is recrystallized from ether/n-hexane

Sources & evidence

ORD record
ord-a08ff052666249a88f230581c05e40af
Source dataset
uspto-grants-1994_02
Patent number
US05283248

Reaction notes

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