Methyl iodide → (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone

HRID 1198293Notes

Reaction equation

HRID 1198293 reaction equation
[F:1][C:2]([F:9])([F:8])[CH2:3][CH2:4][C:5]([OH:7])=O.F[C:11](F)(F)CCC(Cl)=O.C(Cl)(=O)C(Cl)=O.[CH3:25][C@@H:26]1[C@H:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:29][C:28](=[O:37])[N:27]1C(=O)CCC(F)(F)F.C[C@@H]1[C@H](C2C=CC=CC=2)OC(=O)N1.C([Li])CCC.C[Si]([NH-])(C)C.C[Si]([NH-])(C)C.[Na+].[Na+].CI>>[CH3:25][C@@H:26]1[C@H:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[O:29][C:28](=[O:37])[N:27]1[C:5](=[O:7])[C@H:4]([CH3:11])[CH2:3][C:2]([F:1])([F:9])[F:8]

Participants

9

Reactant 8

HCID 6328Methyl iodideHCID 65578Oxalyl chlorideHCID 2733812(4R,5S)-(+)-4-Methyl-5-phenyl-2-oxazolidinoneHCID 27770854,4,4-Trifluorobutanoic acidHCID 11779600HCID 11779600, compoundHCID 151044744,4,4-Trifluorobutanoyl chloride2×HCID 86599718Sodiumbis(trimethylsilylamide)HCID 178418339Butyllithium

Product 1

HCID 10087044(4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone

Procedure

4,4,4-Trifluorobutyric acid may be converted into 4,4,4-trifluorobutyryl chloride by treatment with oxalyl chloride. The 4,4,4-trifluorobutyryl chloride may then be converted into (4R,5S)-4-methyl-3-(4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone by reaction with (4R,5S)-(+)-4-methyl-5-phenyl-2-oxazolidinone in the presence of butyl lithium. The product of this reaction may then be methylated by treatment with sodium bis(trimethylsilylamide) followed by methyl iodide to afford (4R,5S)-4-methyl-3-((2R)-2-methyl-4,4,4-trifluorobutyryl)-5-phenyl-2-oxazolidinone. This product may then be treated with lithium aluminium hydride to afford (R)-2-methyl-4,4,4-trifluorobutan-1-ol. Treatment of this alcohol with phthalimide in the presence of triphenylphosphine and diethyl azodicarboxylate affords (R)-2-(2-methyl-4,4,4-trifluorobutyl)-1H-isoindol-1,3(2H)-dione. Treatment of this product with hydrazine monohydrate followed by hydrochloric acid affords the desired (R)-2-methyl-4,4,4-trifluorobutylamine as the hydrochloride salt.

Workup

  1. customThe product of this reaction

Sources & evidence

ORD record
ord-851b75e0206e4941b17b4f7d6648b130
Source dataset
uspto-grants-1994_01
Patent number
US05280125

Reaction notes

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