Lansoprazole → 4-[2-{3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl-methanesulfinyl}-benzimidazole-1-sulfonyl]-3-isopropyl-5-methylphenoxyacetic acid 2-(toluene-4-sulfonyl)ethyl ester

HRID 2182887Notes

Reaction equation

HRID 2182887 reaction equation
[CH3:1][C:2]1[C:3]([CH2:14][S:15]([C:17]2[NH:21][C:20]3[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=3[N:18]=2)=[O:16])=[N:4][CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].CCN(CC)CC.[C:33]1([CH3:63])[CH:38]=[CH:37][C:36]([S:39]([CH2:42][CH2:43][O:44][C:45](=[O:62])[CH2:46][O:47][C:48]2[CH:53]=[C:52]([CH3:54])[C:51]([S:55](Cl)(=[O:57])=[O:56])=[C:50]([CH:59]([CH3:61])[CH3:60])[CH:49]=2)(=[O:41])=[O:40])=[CH:35][CH:34]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:33]1([CH3:63])[CH:38]=[CH:37][C:36]([S:39]([CH2:42][CH2:43][O:44][C:45](=[O:62])[CH2:46][O:47][C:48]2[CH:53]=[C:52]([CH3:54])[C:51]([S:55]([N:21]3[C:20]4[CH:22]=[CH:23][CH:24]=[CH:25][C:19]=4[N:18]=[C:17]3[S:15]([CH2:14][C:3]3[C:2]([CH3:1])=[C:7]([O:8][CH2:9][C:10]([F:13])([F:11])[F:12])[CH:6]=[CH:5][N:4]=3)=[O:16])(=[O:56])=[O:57])=[C:50]([CH:59]([CH3:60])[CH3:61])[CH:49]=2)(=[O:40])=[O:41])=[CH:35][CH:34]=1

Participants

6

Reactant 4

HCID 3883LansoprazoleHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 865925714-Chlorosulfonyl-3-isopropyl-5-methylphenoxyacetic acid 2-(toluene-4-sulfonyl)ethyl ester2×

Product 1

HCID 207864214-[2-{3-Methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl-methanesulfinyl}-benzimidazole-1-sulfonyl]-3-isopropyl-5-methylphenoxyacetic acid 2-(toluene-4-sulfonyl)ethyl esterYield 79%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a heterogeneous solution of 2-[3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl-methanesulfinyl]-1H-benzimidazole (LANSOPRAZOLE 1.0 g, 2.71 mmol) and 2 mL of Et3N in 20 mL of CH2Cl2 was added 4-chlorosulfonyl-3-isopropyl-5-methylphenoxyacetic acid 2-(toluene-4-sulfonyl)ethyl ester the (Intermediate 65, 1.6 g, 3.25 mmol, 1.2 eq). About 1 g of solid NaHCO3 was added after the chlorosulfonyl ester has dissolved completely in the reaction mixture. The mixture was stirred at room temperature for 2 h. Thereafter the solvent was removed by evaporation and the residual oil was purified by column chromatography (silica gel, CH2Cl2 to 1% MeOH in CH2Cl2) to give 4-[2-{3-methyl-4-(2,2,2-trifluoroethoxy)pyridin-2-yl-methanesulfinyl}-benzimidazole-1-sulfonyl]-3-isopropyl-5-methylphenoxyacetic acid 2-(toluene-4-sulfonyl)ethyl ester (Intermediate 68, 1.76 g, 79%) as a white foam.

Workup

  1. dissolutionhas dissolved completely in the reaction mixture
  2. customThereafter the solvent was removed by evaporation
  3. customthe residual oil was purified by column chromatography (silica gel, CH2Cl2 to 1% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-8b3d31238da8495f90affdacfe965476
Source dataset
uspto-grants-2005_05
Patent number
US06897227B2

Reaction notes

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