Water → Dexlansoprazole

HRID 1609883Notes

Reaction equation

HRID 1609883 reaction equation
[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)=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].O.C(C(C(C(OCC)=O)O)O)(OCC)=[O:27].C(N(C(C)C)CC)(C)C.[O-]O.C1(C(C)C)C=CC=CC=1>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C1(C)C=CC=CC=1>[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)=[O:27])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]([F:12])([F:11])[F:13]

Participants

8

Reactant 5

HCID 962WaterHCID 62333Butanedioic acid, 2,3-dihydroxy-, diethyl ester, S-(R*,R*)-HCID 81531DiisopropylethylamineHCID 1094080Lansoprazole sulfideHCID 53627471Cumen hydroperoxide

Product 1

HCID 9578005Dexlansoprazole

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 1140TolueneSolvent

Conditions

Temperature
52.5 °C

Procedure

Under a nitrogen atmosphere, 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methyl]thio]benzimidazole (50.0 g, 0.14 mol, containing 16.7 mg of water), toluene (100 ml), water (283 mg, 0.016 mol, total water content 0.017 mol) and diethyl (+)-tartrate (10.6 ml, 0.062 mol) were mixed, and the mixture was stirred at 50 to 55° C. for 30 min. Titanium(IV) isopropoxide (8.29 ml, 0.028 mol) was added to the mixture under a nitrogen atmosphere, and the mixture was stirred at 50 to 55° C. for 1 hr. Under a nitrogen atmosphere and under cooling, to the obtained mixture was added diisopropylethylamine (8.13 ml, 0.047 mol) and then cumene hydroperoxide (76.50 ml, content 82%, 0.43 mol) was added at −10 to 0° C. The mixture was reacted by stirring at 0 to 10° C. for 5.5 hr.

Workup

  1. stirringthe mixture was stirred at 50 to 55° C. for 1 hr
  2. temperatureUnder a nitrogen atmosphere and under cooling, to the obtained mixture
  3. customThe mixture was reacted
  4. stirringby stirring at 0 to 10° C. for 5.5 hr

Sources & evidence

ORD record
ord-6d0c9c5241f641ed83b7efba83197096
Source dataset
uspto-grants-2006_01
Patent number
US06982275B2

Reaction notes

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