Water → Dexlansoprazole

HRID 2099868Notes

Reaction equation

HRID 2099868 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

2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]-methyl]thio]benzimidazole (30.0 g, 0.085 mol, containing 31 mg of water), toluene (150 mL), water (59 mg, 0.0033 mol, total amount of water 0.0050 mol) and diethyl (+)-tartrate (3.19 mL, 0.019 mol) were mixed and heated to 50 to 55° C. Titanium (IV) isopropoxide (2.49 mL, 0.0085 mol) was added to the mixture under a nitrogen atmosphere, and the mixture was stirred at 50 to 55° C. for 30 min. Under a nitrogen atmosphere and under cooling, diisopropylethylamine (4.88 mL, 0.028 mol) was added to the obtained mixture and cumene hydroperoxide (46.0 mL, 0.26 mol) was added at −5 to 5° C. The mixture was stirred at −5 to 5° C. for 5.5 hr to allow reaction.

Workup

  1. temperatureUnder a nitrogen atmosphere and under cooling
  2. additionwas added at −5 to 5° C
  3. stirringThe mixture was stirred at −5 to 5° C. for 5.5 hr
  4. customreaction

Sources & evidence

ORD record
ord-a7d4875a61c6437b899d6398bd2b8be5
Source dataset
uspto-grants-2009_08
Patent number
US07569696B2

Reaction notes

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