Hydrochloric Acid → HCID 9843244, compound

HRID 2298040Notes

Reaction equation

HRID 2298040 reaction equation
[C:1]12([CH2:11][NH:12][C:13](=[O:20])[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[ClH:21].N([O-])=O.[Na+].[NH3:26].O>O1CCCC1.O.[Cu]Cl.[Cu](Cl)Cl.ClCCl>[Cl:21][C:15]1[C:16]([N:26]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:1]2)=[CH:17][CH:18]=[CH:19][C:14]=1[C:13]([NH:12][CH2:11][C:1]12[CH2:8][CH:7]3[CH2:6][CH:5]([CH2:4][CH:3]([CH2:9]3)[CH2:2]1)[CH2:10]2)=[O:20]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 3452818HCID 3452818, compoundHCID 12896473Azane;hydrateHCID 23668193Sodium Nitrite

Product 1

HCID 9843244HCID 9843244, compound

Reagents, catalysts & solvents 5

HCID 24014Cupric ChlorideCatalystHCID 62652Cuprous chlorideCatalystHCID 962WaterSolvent3×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-amino-3-(4-{1,1-dimethylethyl}oxycarbonyl]-piperazin-1-yl)-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide (1 g, Example 2a) in tetrahydrofuran (23 ml) was added 1M aqueous hydrochloric acid (2.78 ml) and water (10 ml). The solution was cooled to 0° C. and sodium nitrite (1.91 g) added portion-wise, whilst maintaining the internal temperature below 5° C. After stirring at 0-5° C. for 0.5 h, a pre-cooled suspension of copper (I) chloride (10.58 g) and copper (II) chloride in water (20 ml) was added portion-wise to the pale yellow suspension. The mixture was stirred at 0° C. for 0.5 h then at room temperature for 0.5 h. The reaction mixture was poured into a mixture of water and dichloromethane and 1/1:0.88 ammonia/water was added until the aqueous phase was homogeneous. The layers were separated and the aqueous phase extracted twice further with dichloromethane. The combined organic extracts were washed with 1/1:0.88 ammonia/water until the aqueous layer was colourless, dried over sodium sulfate, filtered and concentrated under reduced pressure to yield an oil. Purification by chromatography on silica gel, eluting with 20-35% ethyl acetate/iso-hexane gave the subtitle compound as a solid (0.45 g).

Workup

  1. temperaturewhilst maintaining the internal temperature below 5° C
  2. additionwas added portion-wise to the pale yellow suspension
  3. stirringThe mixture was stirred at 0° C. for 0.5 h
  4. waitat room temperature for 0.5 h
  5. additionwas added until the aqueous phase
  6. customThe layers were separated
  7. extractionthe aqueous phase extracted twice further with dichloromethane
  8. washThe combined organic extracts were washed with 1/1:0.88 ammonia/water until the aqueous layer
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customto yield an oil
  13. customPurification by chromatography on silica gel
  14. washeluting with 20-35% ethyl acetate/iso-hexane

Sources & evidence

ORD record
ord-eb276152ff5443af9de97b07c01eecd6
Source dataset
uspto-grants-2002_12
Patent number
US06492355B1

Reaction notes

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