Sodium Chloride → Lansoprazole

HRID 428641Notes

Reaction equation

HRID 428641 reaction equation
[CH3:1][C:2]1[C:3]([CH2:14][S:15][C:16]2[NH:20][C:19]3[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=3[N:17]=2)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[OH-].[Na+].ClN1C(=[O:33])CCC1=O.S([O-])([O-])(=O)=S.[Na+].[Na+].[Cl-].[Na+]>C(#N)C.CN(C)C=O.C(OCC)(=O)C.C(O)(=O)C.O>[CH3:1][C:2]1[C:3]([CH2:14][S:15]([C:16]2[NH:17][C:18]3[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=3[N:20]=2)=[O:33])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]([F:12])([F:11])[F:13]

Participants

11

Reactant 5

HCID 5234Sodium ChlorideHCID 14798Sodium HydroxideHCID 24477Sodium ThiosulfateHCID 31398ChlorosuccinimideHCID 1094080Lansoprazole sulfide

Product 1

HCID 3883LansoprazoleYield 84.2%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-{[3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl]methylthio}-1H-benzimidazole (1.0 g, 2.83 mmol) was suspended in 8 ml of acetonitrile, followed by the addition of 3.5 ml of a 2N aqueous solution of sodium hydroxide. A solution (2 ml) of N-chlorosuccinimide (453 mg, 3.40 mmol) in N,N-dimethylformamide was added dropwise to the solution at −4° C. to 3° C. The reaction mixture was subsequently reacted at −3° C. to 0° C. for 1.5 hr. To the reaction mixture was added a 10% aqueous solution of sodium thiosulfate (2 ml) was added to the reaction mixture and the resulting mixture was stirred for 2 min, followed by the addition of water (20 ml) and acetic acid (0.4 ml) to adjust the solution to about pH 8.5. Ethyl acetate (20 ml) and sodium chloride (3 g) were added thereto to extract and the aqueous layer was further extracted with ethyl acetate (10 ml). The organic layers were combined, washed with a 15% aqueous solution of sodium chloride (10 ml) for three times, and the solvent was evaporated. Ethyl acetate (3 ml), hexane (7 ml) and toluene (2.5 ml) were added to the resulting oil, and then stirred at room temperature for 1 hr. The resulting crystals were collected by filtration, washed with a solvent mixture (3 ml) of 30% ethyl acetate and hexane for two times, and then dried under reduced pressure, to give the title compound (0.88 g, yield; 84.1%) as grayish white crystals. 1H-NMR (400 MHz, DMSO-d6); δ (ppm) 2.16(s, 3H), 4.74(d,J=13.7 Hz, 1H), 4.87(d,J=13.7 Hz, 1H), 4.88(d,J=8.8 Hz, 1H), 4.91(d,J=8.8 Hz, 1H), 7.08(d,J=5.9 Hz, 1H), 7.29(m, 2H), 7.56(m, 1H), 7.70(m, 1H), 8.27(d,J=5.9 Hz, 1H), 13.55(s, 1H).

Workup

  1. customThe reaction mixture was subsequently reacted at −3° C. to 0° C. for 1.5 hr
  2. additionwas added to the reaction mixture
  3. extractionto extract
  4. extractionthe aqueous layer was further extracted with ethyl acetate (10 ml)
  5. washwashed with a 15% aqueous solution of sodium chloride (10 ml) for three times
  6. customthe solvent was evaporated
  7. additionEthyl acetate (3 ml), hexane (7 ml) and toluene (2.5 ml) were added to the resulting oil
  8. stirringstirred at room temperature for 1 hr
  9. filtrationThe resulting crystals were collected by filtration
  10. washwashed with a solvent mixture (3 ml) of 30% ethyl acetate and hexane for two times
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-26755e435c184e4993dc3658a0803b64
Source dataset
uspto-grants-2001_11
Patent number
US06313303B1

Reaction notes

Loading…