Hydrochloric Acid → HCID 66599026, compound

HRID 2191209Notes

Reaction equation

HRID 2191209 reaction equation
Cl.[CH3:2][C:3]1[CH:14]=[C:13]([CH3:15])[C:6]2[NH:7][CH2:8][CH2:9][CH2:10][C:11](=[O:12])[C:5]=2[CH:4]=1.CC1CCCO1.O.C([O-])([O-])=O.[Na+].[Na+].Cl[C:30]([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31].Cl>>[CH3:2][C:3]1[CH:14]=[C:13]([CH3:15])[C:6]2[N:7]([C:30]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[O:31])[CH2:8][CH2:9][CH2:10][C:11](=[O:12])[C:5]=2[CH:4]=1

Participants

7

Reactant 6

HCID 313Hydrochloric AcidHCID 962WaterHCID 73012-MethyltetrahydrofuranHCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 573473077,9-Dimethyl-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one--hydrogen chloride (1/1)

Product 1

HCID 66599026HCID 66599026, compoundYield 91.9%

Conditions

Temperature
10 °C

Procedure

Charge a 22 L flask with an overhead stirrer, thermocouple, 3 L addition funnel, baffle, cooling bath and N2 purge and 7,9-dimethyl-3,4-dihydro-1H-benzo[b]azepin-5(2H)-one hydrochloride (1,000 g, 4.43 moles). Add 2-methyltetrahydrofuran (6.44 kg, 7.5 L, 74.5 moles) and agitate the off-white slurry. Cool to 5-15° C. Add water 2.5 L, 138.8 moles and Na2CO3 (1.12 kg, 3 moles) to the addition funnel then slowly add to the reaction mixture at a fast drip over about 25 m. Charge a 2 L addition funnel with benzyl chloroformate (91.59 kg, 8.86 moles) add dropwise to the reaction, while maintaining the reaction mixture below about 15° C. Transfer the resulting mixture to a flask equipped with a condenser and heat to 25-25° C. and stir for about 50 h. Cool to about 15° C., add HCl (5 M, until the pH is about 5). Separate the layers. Extract the aqueous layer with methyltetrahydrofuran (4 L); combine the organic layers and wash with water (4 l). Concentrate the organic layer at about 40° C. Add IPA (4 L) and then concentrate to 2 L. Transfer to a 12 L flask equipped with an overhead stirrer, thermocouple, heating mantle condenser, 2 L addition funnel and N2 purge. Heat the flask contents to about 70-80° C. and add heptane (5 L). Slowly cool to RT overnight; seed the mixture if necessary to induce crystallization of the titled compound. Cool and collect the solid; rinse the solid with cold heptane and dry in a vacuum at 50° C. to provide 1,316 g of the title compound.

Workup

  1. additionCharge a 22 L flask with an overhead stirrer
  2. additionthermocouple, 3 L addition funnel
  3. temperaturebaffle, cooling bath
  4. customN2 purge
  5. additionCharge
  6. additionadd dropwise to the reaction
  7. temperaturewhile maintaining the reaction mixture below about 15° C
  8. customequipped with a condenser
  9. temperatureheat to 25-25° C.
  10. temperatureCool to about 15° C.
  11. customSeparate the layers
  12. extractionExtract the aqueous layer with methyltetrahydrofuran (4 L)
  13. washwash with water (4 l)
  14. concentrationConcentrate the organic layer at about 40° C
  15. concentrationAdd IPA (4 L) and then concentrate to 2 L
  16. customTransfer to a 12 L flask equipped with an overhead stirrer
  17. temperaturethermocouple, heating mantle
  18. additioncondenser, 2 L addition funnel
  19. customN2 purge
  20. temperatureHeat the flask contents to about 70-80° C.
  21. additionadd heptane (5 L)
  22. temperatureSlowly cool to RT overnight
  23. customcrystallization of the titled compound
  24. temperatureCool
  25. customcollect the solid
  26. washrinse the solid with cold heptane
  27. customdry in a vacuum at 50° C.

Sources & evidence

ORD record
ord-b61e665f9d3a4fa8893ccfbfa348fd0d
Source dataset
uspto-grants-2012_12
Patent number
US08329688B2

Reaction notes

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