Sodium Bicarbonate → Liafensine

HRID 1967429Notes

Reaction equation

HRID 1967429 reaction equation
Cl.Cl.[CH3:3][N:4]1[CH2:13][C@@H:12]([C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=2)[C:11]2[C:6](=[CH:7][C:8]([C:24]3[N:29]=[N:28][C:27]([NH2:30])=[CH:26][CH:25]=3)=[CH:9][CH:10]=2)[CH2:5]1.C([O-])(O)=O.[Na+]>CO.O>[CH3:3][N:4]1[CH2:13][C@@H:12]([C:14]2[CH:23]=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=2)[C:11]2[C:6](=[CH:7][C:8]([C:24]3[N:29]=[N:28][C:27]([NH2:30])=[CH:26][CH:25]=3)=[CH:9][CH:10]=2)[CH2:5]1

Participants

4

Reactant 2

HCID 516892Sodium Bicarbonate2×HCID 66911481HCID 66911481, compound

Product 1

HCID 58212050LiafensineYield 9,310.1%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent2×

Procedure

A solution of Compound 13 (30.0 g, 0.68 mmol,) in 1:1 (v/v) MeOH/H2O (900 mL) was filtered through a glass-sintered funnel. The filtrate was then stirred at room temperature as a saturated solution of aqueous NaHCO3 (45 mL) was slowly added over 30 minutes, causing the solution to turn cloudy. Previously prepared seed crystals (0.10 g,) were then added to the batch in one portion. Additional saturated aqueous NaHCO3 (555 mL) was added to the reaction mixture over 1.5 h. The slurry was filtered to afford a wet cake. The wet filter cake was then suspended in 8:2 (v/v) H2O/MeOH (250 mL) and the resulting slurry was stirred for 3 hours and then filtered. The filter cake was washed with 8:2 (v/v) H2O/MeOH (100 mL) and the obtained white solid was dried in vacuo at 50° C. for 30 h to give Compound 2 (23.2 g, 93% yield): 1H NMR (d6-DMSO, 300 MHz) δ 7.80-7.90 (m, 3H), 7.74-7.78 (m, 3H), 7.65 (dd, J=8.6; 2.1 Hz, 1H), 7.43-7.53 (m, 2H), 7.38 (dd, J=8.6; 2.1 Hz, 1H), 6.90 (d, J=8.0 Hz, 1H), 6.83 (d, J=9.1 Hz, 1H), 6.45 (s, 2H), 4.43 (t, J=5.9 Hz, 1H), 3.73 (s, 2H), 3.00 (dd, J=10.7, 5.4 Hz, 1H), 2.70 (dd, J=11.3; 7.5 Hz, 1H), 2.37 (s, 3H); 13C NMR (75 MHz, DMSO) ppm 159.69, 149.65, 142.55, 136.95, 135.62, 134.79, 132.93, 131.83, 129.47, 127.67, 127.46, 127.40, 127.28, 127.16, 125.98, 125.47, 125.15, 123.32, 123.06, 114.12, 60.63, 57.82, 45.55, 44.69, 40.34.

Workup

  1. additionwas slowly added over 30 minutes
  2. additionPreviously prepared seed crystals (0.10 g,) were then added to the batch in one portion
  3. filtrationThe slurry was filtered
  4. customto afford a wet cake
  5. filtrationfiltered
  6. washThe filter cake was washed with 8:2 (v/v) H2O/MeOH (100 mL)
  7. customthe obtained white solid was dried in vacuo at 50° C. for 30 h

Sources & evidence

ORD record
ord-86ac014648af4bb5b87c883135637504
Source dataset
uspto-grants-2013_04
Patent number
US08420811B2

Reaction notes

Loading…