Water → Dexlansoprazole

HRID 1181625Notes

Reaction equation

HRID 1181625 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].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:17][C:18]3[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=3[N:20]=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

Procedure

2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole monohydrate (6 kg, 16.2 mol) was dried in vacuo at 80° C. for 21 hours to give 2-[[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole (5.73 kg, water content 0.0364%). 2-[[[3-Methyl-4-(2,2,2-trifluoroethoxy)-2-pyridinyl]methyl]thio]-1H-benzimidazole (5.00 kg, 14.1 mol, containing water 1.82 g), toluene (25 L), water (13.18 g, 0.732 mol, as total water content 0.833 mol) and (+)-diethyl tartrate (531 mL, 3.10 mol) were mixed under a nitrogen gas stream. Titanium(IV) isopropoxide (414 mL, 1.40 mol) was added at 50-60° C. under a nitrogen gas stream, and the mixture was stirred at the same temperature for 30 min. Diisopropylethylamine (815 mL, 4.68 mol) was added under a nitrogen gas stream at 15-25° C., and cumene hydroperoxide (7.65 L, content 82%, 42.7 mol) was added at −10° C. to 5° C. and the mixture was stirred at −8° C. to 2° C. for 3 hours to allow reaction.

Workup

  1. stirringthe mixture was stirred at −8° C. to 2° C. for 3 hours
  2. customreaction

Sources & evidence

ORD record
ord-355c87ecab1848468ec4048a712a9b69
Source dataset
uspto-grants-2007_10
Patent number
US07285668B2

Reaction notes

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