Tetrahydrofuran → HCID 11961707, compound

HRID 1182349Notes

Reaction equation

HRID 1182349 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH2:10][CH2:9][CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:6]=2[N:19]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:26]1C[O:29][CH2:28][CH2:27]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[O:29]=[CH:28][CH2:27][CH2:26][C:2]1[CH:3]=[CH:4][C:5]2[CH2:11][CH2:10][CH2:9][CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:6]=2[N:19]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 10379064tert-Butyl 2-chloro-7,8-dihydro-5H-pyrido[2,3-b]azepine-9(6H)-carboxylate

Product 1

HCID 11961707HCID 11961707, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
20 °C

Procedure

A suspension of 1,1-dimethylethyl 2-chloro-5,6,7,8-tetrahydro-9H-pyrido[2,3-b]azepine-9-carboxylate (3.32 kg), potassium carbonate (3.25 kg), palladium acetate (132 g) and 1,1′-bis(diphenylphosphanyl)ferrocene (dppf) ((326 g) in THF (16.5 L) was degassed and put under an atmosphere of nitrogen. The THF solution of the hydroborated acrolein acetal was then added. The reaction mixture was degassed, purged with nitrogen and then heated at reflux for 26 hours. The reaction mixture was then cooled to 20° C., water (66 L) was added and the mixture was stirred for 30 minutes. The two layers were allowed to settle and the lower aqueous phase was discarded. IPAc (10 L) was then added and, after stirring for 5 minutes and allowing the mixture to settle, the lower aqueous phase was again discarded. The resulting organic layer was concentrated by distillation under reduced pressure to minimum volume (55 L of distillate removed) and a second portion of IPAc (33 L) was then charged. The two layers were again separated, the aqueous phase was discarded and the remaining organic layer was concentrated to minimum volume (10 L) under reduced pressure. IPAc (23 L) was added and the mixture held overnight at ambient temperature. The solution was cooled to 0° C. and treated with pre-cooled (0° C.) 2M hydrochloric acid (23.0 L), while keeping the temperature below 10° C. The resulting two phase mixture was stirred at 0° C. for 4 hours.

Workup

  1. customwas degassed
  2. additionThe THF solution of the hydroborated acrolein acetal was then added
  3. customThe reaction mixture was degassed
  4. custompurged with nitrogen
  5. temperatureheated
  6. temperatureat reflux for 26 hours
  7. additionwater (66 L) was added
  8. additionIPAc (10 L) was then added
  9. stirringafter stirring for 5 minutes
  10. concentrationThe resulting organic layer was concentrated by distillation under reduced pressure to minimum volume (55 L of distillate removed)
  11. additiona second portion of IPAc (33 L) was then charged
  12. customThe two layers were again separated
  13. concentrationthe remaining organic layer was concentrated to minimum volume (10 L) under reduced pressure
  14. additionIPAc (23 L) was added
  15. waitthe mixture held overnight at ambient temperature
  16. temperatureThe solution was cooled to 0° C.
  17. additiontreated
  18. temperaturewith pre-cooled (0° C.) 2M hydrochloric acid (23.0 L)
  19. customthe temperature below 10° C
  20. stirringThe resulting two phase mixture was stirred at 0° C. for 4 hours

Sources & evidence

ORD record
ord-c7655c590142496eb108ae783765abb2
Source dataset
uspto-grants-2007_10
Patent number
US07288655B2

Reaction notes

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