Triethylamine → HCID 136333952, compound

HRID 1022964Notes

Reaction equation

HRID 1022964 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:13]([C:14](O)=O)[C@H:12]2[CH2:17][C@@H:9]1[CH2:10][C@H:11]2[F:18])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.C(Cl)(=O)OCC(C)C.[NH2:34][C:35]1[CH:39]=[C:38]([Br:40])[S:37][C:36]=1[C:41]([NH2:43])=[O:42]>O1CCCC1.O>[Br:40][C:38]1[S:37][C:36]2[C:41](=[O:42])[NH:43][C:14]([C@@H:13]3[C@H:12]4[CH2:17][C@H:9]([CH2:10][C@H:11]4[F:18])[N:8]3[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])=[N:34][C:35]=2[CH:39]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 219758623-Amino-5-bromothiophene-2-carboxamideHCID 71147492HCID 71147492, compound

Product 1

HCID 136333952HCID 136333952, compoundYield 68.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (1R*,3S,4R*,5R)-2-(tert-butoxycarbonyl)-5-fluoro-2-azabicyclo[2.2.1]heptane-3-carboxylic acid (352 mg) and triethylamine (0.190 mL) in tetrahydrofuran (4 mL) was added 2-methylpropyl chlorocarbonate (0.178 mL) at 0° C., and the mixture was stirred at room temperature for 30 min. To the reaction system was added a solution of 3-amino-5-bromothiophene-2-carboxamide (200 mg) produced in Example 1, step D, in tetrahydrofuran (2 mL), and the mixture was stirred at 60° C. for 18 hr. Water was added to the reaction mixture, and the separated aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. Insoluble material was filtered off, the filtrate was concentrated under reduced pressure, and the residue was purified by basic silica gel column chromatography (ethyl acetate/hexane). To the obtained pale-yellow solid (328 mg) were added 2M aqueous sodium hydroxide solution (1.81 mL) and ethanol (4.0 mL), and the mixture was stirred at 70° C. for 5 hr. The reaction system was neutralized with 1M hydrochloric acid at 0° C. To the reaction system was added water (2 mL), and the precipitate was collected by filtration to give the title compound (274 mg) as a colorless solid.

Workup

  1. extractionthe separated aqueous layer was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationInsoluble material was filtered off
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by basic silica gel column chromatography (ethyl acetate/hexane)
  7. additionTo the obtained pale-yellow solid (328 mg) were added 2M aqueous sodium hydroxide solution (1.81 mL) and ethanol (4.0 mL)
  8. stirringthe mixture was stirred at 70° C. for 5 hr
  9. customwas neutralized with 1M hydrochloric acid at 0° C
  10. additionTo the reaction system was added water (2 mL)
  11. filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record
ord-a0c51e3f1aa74bcf915201b053b9eb05
Source dataset
uspto-grants-2014_05
Patent number
US08722660B2

Reaction notes

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