Hydrochloric Acid → HCID 178461482, compound

HRID 2097678Notes

Reaction equation

HRID 2097678 reaction equation
[O:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[N:15]=[N:16][NH:17][C:18]=1[C:19]([O:21]CC)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Li+].Cl.[CH3:27][C@H:28]1[C@H:36]([NH2:37])[CH2:35][C@H:31]2[C:32]([CH3:34])([CH3:33])[C@@H:29]1[CH2:30]2.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O.[Cl-].[Na+].O.CN(C=O)C.CCOC(C)=O.C1COCC1.CO>[O:1]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[N:15]=[N:16][NH:17][C:18]=1[C:19]([NH:37][C@@H:36]1[CH2:35][C@H:31]2[CH2:30][C@@H:29]([C:32]2([CH3:34])[CH3:33])[C@H:28]1[CH3:27])=[O:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

12

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11744832(1R,2R,3R,5S)-2,6,6-Trimethylbicyclo[3.1.1]heptan-3-amineHCID 178470429HCID 178470429, compound

Product 1

HCID 178461482HCID 178461482, compound

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21899815MeOH tetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent2×

Conditions

Temperature
50 °C

Procedure

A solution of ester (9) (1.0 equiv) in 2.5:1 THF/MeOH (0.5 M) was treated with a solution of lithium hydroxide (3.0 equiv) in water (1.6 M), and the resulting mixture was stirred at 50° C. overnight, cooled to room temperature, acidified with 1M HCl, diluted with brine and extracted with AcOEt (3×). The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The pale yellow foam obtained was dissolved in dry DMF (0.4 M) and treated with (−)-isopinocampheyl amine (12) (1.0 equiv), followed by triethylamine (1.0 equiv) and HBTU (1.0 equiv). The resulting solution was stirred at rt for 1 h, diluted with brine and AcOEt. The layers were separated and the aqueous one was washed with brine (2×), 1M HCl and brine (2×), dried (MgSO4), filtered and concentrated under reduced pressure to provide 4-(2-phenoxyphenyl)-N-((1R,2R,3R,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl)-1H-1,2,3-triazole-5-carboxamide (13) as a pale yellow foam and was used without further purification.

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with AcOEt (3×)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe pale yellow foam obtained
  8. stirringThe resulting solution was stirred at rt for 1 h
  9. customThe layers were separated
  10. washthe aqueous one was washed with brine (2×), 1M HCl and brine (2×)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ef10f19995b446e8b6b78aa0ab190155
Source dataset
uspto-grants-2013_05
Patent number
US08450350B2

Reaction notes

Loading…