2-Fluoro-1H-imidazole hydrochloride → (R)-3-hydroxy-2-[2-(imidazol-2-ylamino)-2-(3-methyl-1,2,4-oxadiazol-5-yl)-ethylsulfanylmethyl]-5-methoxy-6-methyl-benzoic acid methyl ester hydrochloride

HRID 234242Notes

Reaction equation

HRID 234242 reaction equation
[CH3:1][O:2][C:3](=[O:34])[C:4]1[C:9]([CH3:10])=[C:8]([O:11][CH3:12])[CH:7]=[C:6]([O:13][Si](C)(C)C(C)(C)C(C)C)[C:5]=1[CH2:23][S:24][CH2:25][C@H:26]([NH2:33])[C:27]1[O:31][N:30]=[C:29]([CH3:32])[N:28]=1.[ClH:35].F[C:37]1[NH:38][CH:39]=[CH:40][N:41]=1>CN(C)C=O>[ClH:35].[CH3:1][O:2][C:3](=[O:34])[C:4]1[C:9]([CH3:10])=[C:8]([O:11][CH3:12])[CH:7]=[C:6]([OH:13])[C:5]=1[CH2:23][S:24][CH2:25][C@H:26]([NH:33][C:37]1[NH:38][CH:39]=[CH:40][N:41]=1)[C:27]1[O:31][N:30]=[C:29]([CH3:32])[N:28]=1

Participants

4

Reactant 2

HCID 126246272-Fluoro-1H-imidazole hydrochloride2×HCID 53739152(R)-2-[2-amino-2-(3-methyl-1,2,4-oxadiazol-5-yl)-ethylsulfanyl-methyl]-3-[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxy]-5-methoxy-6-methyl-benzoic acid methyl ester

Product 1

HCID 86750115(R)-3-hydroxy-2-[2-(imidazol-2-ylamino)-2-(3-methyl-1,2,4-oxadiazol-5-yl)-ethylsulfanylmethyl]-5-methoxy-6-methyl-benzoic acid methyl ester hydrochlorideYield 34.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 985 mg of (R)-2-[2-amino-2-(3-methyl-1,2,4-oxadiazol-5-yl)-ethylsulfanyl-methyl]-3-[dimethyl-(1,1,2-trimethylpropyl)-silanyloxy]-5-methoxy-6-methyl-benzoic acid methyl ester and 237 mg of 2-fluoroimidazole hydrochloride in 5 ml of N,N-dimethylformamide were stirred under argon at 50° C. for 3 h. A second portion of 117 mg of 2-fluoroimidazole hydrochloride was added and stirring was continued for 6 h. The reaction mixture was cooled and the solvent evaporated in vacuo. The residue was purified by silica gel chromatography using methanol/dichloromethane (1:20, v/v) as eluent to yield 310 mg of (R)-3-hydroxy-2-[2-(imidazol-2-ylamino)-2-(3-methyl-1,2,4-oxadiazol-5-yl)-ethylsulfanylmethyl]-5methoxy-6-methyl-benzoic acid methyl ester hydrochloride as yellow solid.

Workup

  1. temperatureThe reaction mixture was cooled
  2. customthe solvent evaporated in vacuo
  3. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-c555e12c45d145cd8093399e50b71070
Source dataset
uspto-grants-1997_01
Patent number
US05594135

Reaction notes

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