Citric Acid → HCID 23653609, compound

HRID 423212Notes

Reaction equation

HRID 423212 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:26]=1)[O:7][CH2:8][C:9]1[N:25]=[CH:24][CH:23]=[CH:22][C:10]=1/[C:11]/2=[C:12](\[C:15]1[CH:16]=[C:17]([NH2:21])[CH:18]=[CH:19][CH:20]=1)/[CH2:13][CH3:14].N1C=CC=CC=1.[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.C(O)(C)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2=[C:6]([CH:26]=1)[O:7][CH2:8][C:9]1[N:25]=[CH:24][CH:23]=[CH:22][C:10]=1/[C:11]/2=[C:12](\[C:15]1[CH:16]=[C:17]([NH:21][S:34]([CH3:33])(=[O:36])=[O:35])[CH:18]=[CH:19][CH:20]=1)/[CH2:13][CH3:14]

Participants

7

Reactant 4

HCID 311Citric AcidHCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 59242946HCID 59242946, compound

Product 1

HCID 23653609HCID 23653609, compoundYield 71.5%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

Under a nitrogen atmosphere, solid (E)-3-[1-(8-chloro-11H-10-oxa-1-aza-dibenzo[a,d]cyclohepten-5-ylidene)-propyl]-phenylamine (198 g, 545 mmol), pyridine (67.0 mL, 828 mmol) and dichloromethane (1.6 L) are charged to a 5 liter 4 neck round bottom flask equipped with a mechanical stirrer and thermocouple. To the dark green reaction mixture, a solution of methanesulfonyl chloride (51.0 mL, 658 mmol) in dichloromethane (400 mL) is added dropwise over 20 min from an addition funnel. An exotherm of 6.9° C. is observed over the course of the addition. Upon completion of addition the reaction is stirred for 16 h at ambient temperature. The mixture is charged to a 22 L bottom outlet flask containing 10% citric acid solution (2 L). The mixture is stirred for 15 min and the layers separated upon standing. The organic layer is washed with a 15% NaCl solution. The organic layer is charged to a 5 L 4 neck flask, equipped with a mechanical stirrer under a nitrogen atmosphere. The deep red solution is treated with DARCO® activated charcoal (200 g), Na2SO4 (200 g) and TMT (trithiocyanuric acid trisodium salt hydrate) (50 g). The mixture is stirred for 18 h at ambient temperature and then filtered over a 2 in (about 5 cm) pad of diatomaceous earth (Hy-flo Supercel®). The filtrate is concentrated in vacuo yielding a hard white foam. Isopropyl alcohol (1 L, 5 volumes) is added to the foam and the slurry is stirred at 40° C. for one hour. The thick mixture is cooled to ambient temperature. The solids are vacuum filtered over a polypropylene pad in a buchner funnel The material is dried at 70° C. for 16 h under house vacuum yielding 171.85 g (71.4%) of white crystalline product. LC-ES/MS m/e 441.2 [M+H]+, 439.1 [M−H]−. Anal. Calcd for C23H21N2ClO3S: C, 62.65; H, 4.80; N, 6.35. Found: C, 62.81; H, 4.82; N, 6.20.

Workup

  1. customequipped with a mechanical stirrer
  2. additionAn exotherm of 6.9° C. is observed over the course of the addition
  3. additionUpon completion of addition the reaction
  4. additionThe mixture is charged to a 22 L bottom outlet flask
  5. stirringThe mixture is stirred for 15 min
  6. customthe layers separated
  7. washThe organic layer is washed with a 15% NaCl solution
  8. additionThe organic layer is charged to a 5 L 4 neck flask
  9. customequipped with a mechanical stirrer under a nitrogen atmosphere
  10. additionThe deep red solution is treated with DARCO® activated charcoal (200 g), Na2SO4 (200 g) and TMT (trithiocyanuric acid trisodium salt hydrate) (50 g)
  11. stirringThe mixture is stirred for 18 h at ambient temperature
  12. filtrationfiltered over a 2 in (about 5 cm) pad of diatomaceous earth (Hy-flo Supercel®)
  13. concentrationThe filtrate is concentrated in vacuo
  14. customyielding a hard white foam
  15. stirringthe slurry is stirred at 40° C. for one hour
  16. temperatureThe thick mixture is cooled to ambient temperature
  17. filtrationfiltered over a polypropylene pad in a buchner funnel The material
  18. customis dried at 70° C. for 16 h under house vacuum

Sources & evidence

ORD record
ord-6b0e2b5206c04b71afa4afd3928d34d1
Source dataset
uspto-grants-2012_01
Patent number
US08101760B2

Reaction notes

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