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 1082181Notes

Reaction equation

HRID 1082181 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-trimethyl-propyl) -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]-5-methoxy-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-38c12cb9a4094c288fb6d29e763a4659
Source dataset
uspto-grants-1996_12
Patent number
US05589473

Reaction notes

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