Sodium Hydroxide → HCID 178457028, compound

HRID 1655605Notes

Reaction equation

HRID 1655605 reaction equation
[CH2:1]([N:4]([C:42]1[C:47]([C:48]([O:50]CC)=[O:49])=[CH:46][C:45]([C:53]([F:56])([F:55])[F:54])=[CH:44][N:43]=1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]2[N:22](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:21]=[N:20][N:19]=2)=[CH:8][CH:7]=1)[CH2:2][CH3:3].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[OH-].[Na+]>CO>[CH2:1]([N:4]([C:42]1[C:47]([C:48]([OH:50])=[O:49])=[CH:46][C:45]([C:53]([F:54])([F:55])[F:56])=[CH:44][N:43]=1)[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:18]2[NH:22][N:21]=[N:20][N:19]=2)=[CH:8][CH:7]=1)[CH2:2][CH3:3]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 521998p-Toluenesulfonic acid monohydrateHCID 19791962HCID 19791962, compound

Product 1

HCID 178457028HCID 178457028, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

Ethyl 5-iodopyridin-2-one-3-carboxylate, prepared by the method of Taylor, J. Org. Chem. 54, 36 (1989), is treated with tert-butyldimethylsilyl chloride (TBSCl) in methylene chloride containing triethylamine to give the O-silylated pyridine. Treatment of ethyl 2-tert-butyldimethylsilyloxy-5-iodopyridine-3-carboxylate with bis(trifluoromethyl)cadmium in the presence of copper (I) bromide in dimethylformamide gives the ethyl 2-tert-butyldimethylsilyloxy-5-trifluoromethylpyridine-3-carboxylate compound. Treatment of the silyloxy compound with aqueous hydrochloric acid in tetrahydrofuran removes the silyl protecting group. Treatment of ethyl 2-hydroxy-5-trifluoromethylpyridine-3-carboxylate with phosphorus oxychloride affords the 2-chloro compound. Treatment of ethyl 2-chloro-5-trifluoromethylpyridine-3-carboxylate with N-triphenylmethyl-5-[2-(4'-propylaminomethyl-biphenyl)]tetrazole, prepared as described in Example 72B, in tetrahydrofuran containing triethylamine affords the tertiary amine. Treatment of ethyl 2-{N-propyl-N-[(2'-[N-triphenylmethyl-1H-tetrazol-5-yl]biphenyl-4-yl)methyl]amino}-5-trifluoromethyl-pyridine-3-carboxylate with p-toluenesulfonic acid monohydrate in methanol to detritylate followed by sodium hydroxide in methanol hydrolysis gives the title compound.

Sources & evidence

ORD record
ord-7389e65f862b46d6be9c256b8c56203a
Source dataset
uspto-grants-1993_10
Patent number
US05250548

Reaction notes

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