Triethylamine → HCID 136333940, compound

HRID 1022947Notes

Reaction equation

HRID 1022947 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][C:12]([CH3:15])([CH3:14])[O:11][CH2:10][CH:9]1[C:16](O)=O)=[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:16]([CH:9]3[N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][C:12]([CH3:14])([CH3:15])[O:11][CH2:10]3)=[N:34][C:35]=2[CH:39]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 62365Isobutyl chloroformateHCID 219758623-Amino-5-bromothiophene-2-carboxamideHCID 50999109HCID 50999109, compound

Product 1

HCID 136333940HCID 136333940, compoundYield 55.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

To a solution of 4-(tert-butoxycarbonyl)-6,6-dimethylmorpholine-3-carboxylic acid (1.00 g) and triethylamine (1.08 mL) in tetrahydrofuran (20 mL) was added, while stirring under ice-cooling, 2-methylpropyl chlorocarbonate (0.50 mL). After stirring at room temperature for 30 min, a solution of 3-amino-5-bromothiophene-2-carboxamide (568 mg) produced in Example 1, step D, in tetrahydrofuran (3 mL) was added. The reaction system was stirred with heating at 60° C. for 3 hr. Water was poured into the reaction system, and the mixture was extracted with ethyl acetate, washed with brine, and dried over anhydrous magnesium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. To the residue were added 2M aqueous sodium hydroxide solution (7.7 mL) and ethanol (20 mL), and the mixture was stirred with heating at 80° C. for 5 hr. Brine was poured into the reaction system, the mixture was extracted with 3:1 ethyl acetate/tetrahydrofuran mixture, and the extract was washed with brine, and dried over anhydrous magnesium sulfate. Insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (methanol/ethyl acetate) to give the title compound (630 mg) as a white solid.

Workup

  1. temperaturecooling
  2. stirringAfter stirring at room temperature for 30 min
  3. stirringThe reaction system was stirred
  4. extractionthe mixture was extracted with ethyl acetate
  5. washwashed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customInsoluble material was removed by filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. additionTo the residue were added 2M aqueous sodium hydroxide solution (7.7 mL) and ethanol (20 mL)
  10. stirringthe mixture was stirred
  11. temperaturewith heating at 80° C. for 5 hr
  12. additionBrine was poured into the reaction system
  13. extractionthe mixture was extracted with 3:1 ethyl acetate/tetrahydrofuran mixture
  14. washthe extract was washed with brine
  15. dry with materialdried over anhydrous magnesium sulfate
  16. customInsoluble material was removed by filtration
  17. concentrationthe filtrate was concentrated under reduced pressure
  18. customThe residue was purified by basic silica gel column chromatography (methanol/ethyl acetate)

Sources & evidence

ORD record
ord-7ca68eae42944f99bba76a24086e310a
Source dataset
uspto-grants-2014_05
Patent number
US08722660B2

Reaction notes

Loading…