Hydrochloric Acid → HCID 69152414, compound

HRID 2375349Notes

Reaction equation

HRID 2375349 reaction equation
[C:1]([C:5]1[CH:14]=[C:13]2[C:8]([CH2:9][CH2:10][NH:11][CH2:12]2)=[CH:7][CH:6]=1)(=[O:4])[CH2:2][CH3:3].[OH-].[Na+].Br[CH2:18][CH2:19][CH2:20][Cl:21].C(N(CC)CC)C.Cl>ClCCl.C(O)(C)C.O>[Cl:21][CH2:20][CH2:19][CH2:18][N:11]1[CH2:10][CH2:9][C:8]2[C:13](=[CH:14][C:5]([C:1](=[O:4])[CH2:2][CH3:3])=[CH:6][CH:7]=2)[CH2:12]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 80061-Bromo-3-chloropropaneHCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 58508982HCID 58508982, compound

Product 1

HCID 69152414HCID 69152414, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent

Procedure

The isomer mixture from step 1.3 (0.27 mol, 63.4 g) was suspended in 634 ml of dichloromethane. The base was liberated from the hydrochloride by adding 1.05 eq of sodium hydroxide solution and 317 ml of water and separating the phases. After phase separation and extraction of the aqueous phase with a little dichloromethane, the combined organic phases were washed once with 50 ml of water, filtered and concentrated several times in a rotary evaporator. The residue was dissolved in dimethylformamide, and 1-bromo-3-chlorpropane (0.68 mol, 107.4 g) and triethylamine (0.55 mol, 55.3 g) were added successively to the solution. It was then stirred at room temperature for 16 h, 760 ml of water were added to the resulting suspension, and it was extracted twice with about 300 ml of dichloromethane. The combined organic phases were washed once with 100 ml of water, filtered and concentrated under reduced pressure. The residue was dissolved in 61 ml of methanol and 410 ml of methyl tert-butyl ether. 1.2 equivalents of hydrogen chloride in isopropanol are added drop-wise thereto. The mixture was briefly boiled and then slowly cooled to room temperature. The precipitate was filtered filtered off sucked air through until it was good. This resulted in 87 g of crude product which was recrystallized twice from methanol. This resulted in 26.7 g of the title compound (7 isomer:6 isomer: 97:3 (via 13C-NMR)).

Workup

  1. customseparating the phases
  2. customAfter phase separation and extraction of the aqueous phase with a little dichloromethane
  3. washthe combined organic phases were washed once with 50 ml of water
  4. filtrationfiltered
  5. concentrationconcentrated several times
  6. customin a rotary evaporator
  7. dissolutionThe residue was dissolved in dimethylformamide
  8. extractionwas extracted twice with about 300 ml of dichloromethane
  9. washThe combined organic phases were washed once with 100 ml of water
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe residue was dissolved in 61 ml of methanol
  13. temperatureslowly cooled to room temperature
  14. filtrationThe precipitate was filtered
  15. filtrationfiltered off
  16. customThis resulted in 87 g of crude product which
  17. customwas recrystallized twice from methanol

Sources & evidence

ORD record
ord-a5c8f60bf3c54e8c9d64a92a81f0f120
Source dataset
uspto-grants-2008_12
Patent number
US07465744B2

Reaction notes

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