Phthalic Anhydride → HCID 57926052, compound

HRID 1363031Notes

Reaction equation

HRID 1363031 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][OH:6].[C:7]1(=[O:17])[O:12][C:10](=O)[C:9]2=[CH:13][CH:14]=[CH:15][CH:16]=[C:8]12.[CH2:18]([S:20](Cl)(=[O:22])=[O:21])[CH3:19]>C1(C)C=CC=CC=1.CCCCCC.C(N(CC)CC)C.O>[CH2:18]([S:20]([O:6][CH2:5][CH2:4][CH2:3][CH2:2][N:1]1[C:7](=[O:17])[C:8]2[C:9](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:10]1=[O:12])(=[O:22])=[O:21])[CH3:19]

Participants

8

Reactant 3

HCID 6811Phthalic AnhydrideHCID 11667Ethanesulfonyl chlorideHCID 258684-Amino-1-butanol

Product 1

HCID 57926052HCID 57926052, compoundYield 78.36%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 8058HexaneSolventHCID 8471TriethylamineSolvent2×

Conditions

Temperature
85 °C

Procedure

To a solution of 4-aminobutanol (commercially available, for example, from Aldrich) (2.6 kg, 1 eqv) in toluene (65 L, 25 vol) at 25-35° C. was added phthalic anhydride (commercially available, for example, from Aldrich) (4.3 kg, 1 eqv). The temperature of the reaction mixture was slowly raised to 80-90° C. for 2-3 hr and then heated to reflux to azeotropically remove the water from the reaction mass. The progress of the reaction was monitored by TLC, and after passing the TLC (starting material not more than 2%), approximately 25-40% of toluene was removed from reaction by atmospheric distillation. The reaction mass was then cooled to 0-5° C. and triethylamine (4.4 kg, 1.5 eqv) was charged to the reaction mass over 15 min. Ethane sulphonyl chloride (commercially available, for example, from Aldrich) (4.5 kg, 1.2 eqv) diluted in toluene (7.8 L, 3 vol) was slowly added into the reaction mass at 0-5° C. under a nitrogen atmosphere. The reaction mixture was stirred for approximately 2 hr, then monitored by HPLC (starting material not more than 2%). After completion of reaction, water (26 L, 10 vol) and triethylamine (2.6 kg, 1 vol) was added to the reaction mass, and stirred at 30-35° C. for 10-30 min, and then filtered over celite (1.3 kg, 0.5 wt, pre-conditioned with toluene, 2.6 L, 1 vol). The celite was then washed with hot toluene (40-50° C., 10.4 L, 4 vol), and the organic layer was separated. The aqueous layer was extracted with toluene (7.8 L, 3 vol) and combined organic layers were then washed with aqueous sodium bicarbonate solution (2.6 kg in 26 L water) and water (13 L, 5 vol). The organic layer was concentrated in vacuo (vacuum no less than 600 mm Hg), keeping the temperature below 70° C. Iso-propylalcohol (7.8 L, 3 vol) was added and the reaction mass was concentrated in vacuo (vacuum no less than 600 mm Hg), keeping the temperature below 70° C. To this concentrated mass, iso-propylalcohol (26 L, 10 vol) was added, and warmed to 50-60° C. to give a clear solution. This solution was cooled to 35-45° C. and n-hexane (26 L, 10 vol) was added slowly and then cooled to 25-35° C. The reaction mass was stirred for 1.5 to 2.5 hr and filtered by centrifugation. The wet cake was washed with n-hexane (31 L, 11.9 vol) and filtered again by centrifugation. The material was dried in vacuo (vacuum no less than 650 mm Hg) for 10-12 hr at 50-55° C. The title compound was isolated in 78.36% yield (7.1 kg) and 99.6% purity.

Workup

  1. customat 25-35° C.
  2. temperatureheated
  3. temperatureto reflux
  4. customto azeotropically remove the water from the reaction mass
  5. customwas removed from reaction by atmospheric distillation
  6. temperatureThe reaction mass was then cooled to 0-5° C.
  7. additionwas slowly added into the reaction mass at 0-5° C. under a nitrogen atmosphere
  8. additionwas added to the reaction mass
  9. stirringstirred at 30-35° C. for 10-30 min
  10. filtrationfiltered over celite (1.3 kg, 0.5 wt, pre-conditioned with toluene, 2.6 L, 1 vol)
  11. washThe celite was then washed with hot toluene (40-50° C., 10.4 L, 4 vol)
  12. customthe organic layer was separated
  13. extractionThe aqueous layer was extracted with toluene (7.8 L, 3 vol)
  14. washwere then washed with aqueous sodium bicarbonate solution (2.6 kg in 26 L water) and water (13 L, 5 vol)
  15. concentrationThe organic layer was concentrated in vacuo (vacuum no less than 600 mm Hg)
  16. customthe temperature below 70° C
  17. additionIso-propylalcohol (7.8 L, 3 vol) was added
  18. concentrationthe reaction mass was concentrated in vacuo (vacuum no less than 600 mm Hg)
  19. customthe temperature below 70° C
  20. additionTo this concentrated mass, iso-propylalcohol (26 L, 10 vol) was added
  21. temperaturewarmed to 50-60° C.
  22. customto give a clear solution
  23. temperatureThis solution was cooled to 35-45° C.
  24. temperaturecooled to 25-35° C
  25. stirringThe reaction mass was stirred for 1.5 to 2.5 hr
  26. filtrationfiltered by centrifugation
  27. washThe wet cake was washed with n-hexane (31 L, 11.9 vol)
  28. filtrationfiltered again by centrifugation
  29. customThe material was dried in vacuo (vacuum no less than 650 mm Hg) for 10-12 hr at 50-55° C

Sources & evidence

ORD record
ord-d1e410d814a248a5b11da2f1ef82f84a
Source dataset
uspto-grants-2011_02
Patent number
US07884114B2

Reaction notes

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