P,P-Diphenylphosphinic azide → 1-Azabicyclo[3.2.1]oct-5-ylmethyl (5-phenyl-1,3-thiazol-4-yl)carbamate hydrochloride

HRID 383955

Reaction equation

HRID 383955 reaction equation
[C:1]1([C:7]2[S:11][CH:10]=[N:9][C:8]=2C(O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1C=CC(P([N:29]=[N+]=[N-])(C2C=CC=CC=2)=O)=CC=1.[N:32]12[CH2:39][C:36]([CH2:40][OH:41])([CH2:37][CH2:38]1)[CH2:35][CH2:34][CH2:33]2.[ClH:42].[O:43]1[CH2:48]COCC1>C1(C)C=CC=CC=1.CCOC(C)=O.O.CN(C=O)C>[ClH:42].[C:1]1([C:7]2[S:11][CH:10]=[N:9][C:8]=2[NH:29][C:48](=[O:43])[O:41][CH2:40][C:36]23[CH2:39][N:32]([CH2:38][CH2:37]2)[CH2:33][CH2:34][CH2:35]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

9

Reactant 4

HCID 199401P,P-Diphenylphosphinic azideHCID 9448135-phenyl-1,3-thiazole-4-carboxylic AcidHCID 19795992{1-Azabicyclo[3.2.1]octan-5-yl}methanolHCID 204431481,4-Dioxane hydrochloride

Product 1

HCID 866410701-Azabicyclo[3.2.1]oct-5-ylmethyl (5-phenyl-1,3-thiazol-4-yl)carbamate hydrochloride

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-phenyl-1,3-thiazole-4-carboxylic acid (400 mg) in toluene (5 mL) was added TEA (380 μL) at room temperature. To the reaction liquid was added dropwise a solution of DPPA (546 μL) in toluene (5 mL), followed by stirring at the same temperature for 20 minutes. After stirring at 90° C. for 5 minutes, a mixture of 1-azabicyclo [3.2.1]oct-5-yl methanol (357 mg) and DMF (2 mL) was added thereto, followed by heating under reflux for 1 hour. To the reaction liquid was added water, followed by extraction with EtOAc. The organic layer was washed with water and brine in this order, dried over MgSO4, and then concentrated under reduced pressure. The residue was purified by medium-pressure preparative liquid chromatography (YAMAZEN YFLC WPrep2XY, CHCl3:MeOH:28% aqueous ammonia=80:10:1) to obtain an oily substance. This was dissolved in EtOAc, followed by addition of 4 M HCl/dioxane at room temperature. The solid precipitated was collected by filtration and washed with EtOAc to obtain 1-azabicyclo[3.2.1]oct-5-ylmethyl (5-phenyl-1,3-thiazol-4-yl)carbamate hydrochloride (174 mg) as a white solid.

Workup

  1. customTo the reaction liquid
  2. stirringAfter stirring at 90° C. for 5 minutes
  3. additionwas added
  4. temperatureby heating
  5. temperatureunder reflux for 1 hour
  6. customTo the reaction liquid
  7. extractionfollowed by extraction with EtOAc
  8. washThe organic layer was washed with water and brine in this order
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by medium-pressure preparative liquid chromatography (YAMAZEN YFLC WPrep2XY, CHCl3:MeOH:28% aqueous ammonia=80:10:1)
  12. customto obtain an oily substance
  13. customThe solid precipitated
  14. filtrationwas collected by filtration
  15. washwashed with EtOAc

Sources & evidence

ORD record
ord-c953148599a54aacbf477b9c834aa32d
Source dataset
uspto-grants-2013_02
Patent number
US08367696B2

Linked notes

Loading…