Réaction #8281

Équation de réaction

N,N-diisopropylethylamine

3-hydroxypropionic acid

3-(4-(1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)(N-(t-butoxy-carbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one hydrochloride

O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate

→

title product

Rendement 74.2%

3-(4-(1-(3-Hydroxypropanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)-(N-(t-butoxycarbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one

Rendement 74.2%

Solvants

water

ethyl acetate

N,N dimethylformamide

Conditions de réaction

Traitement

1. 1
   TempératureThe mixture was cooled to 0°
2. 2
   Autrethe organic layer separated
3. 3
   Lavagewashed with aqueous sodium dihydrogen phosphate (2%, 40 ml), sodium bicarbonate (40 ml) and brine (40 ml)
4. 4
   AutreSolvent was removed
5. 5
   Autrethe residue chromatographed on a 10 g silica Mega Bond Elut® column
6. 6
   Lavageeluting with a mixture of 2.5% methanol in dichloromethane
7. 7
   Autreevaporated

Mode opératoire

To a solution of 3-hydroxypropionic acid (45 mg, 0.5 mM) in N,N dimethylformamide (2 ml) was added 3-(4-(1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-5(R)(N-(t-butoxy-carbonyl)isoxazol-3-ylaminomethyl)oxazolidin-2-one hydrochloride (256 mg, 0.5 mM, reference example 10), and O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (190 mg, 0.5 mM). The mixture was cooled to 0°, N,N-diisopropylethylamine (129 mg, 1 mM) added, and the mixture stirred 18 hours, allowing the temperature to rise to ambient. The mixture was poured into a mixture of ethyl acetate (40 ml) and water (40 ml), the organic layer separated and washed with aqueous sodium dihydrogen phosphate (2%, 40 ml), sodium bicarbonate (40 ml) and brine (40 ml). Solvent was removed, and the residue chromatographed on a 10 g silica Mega Bond Elut® column, eluting with a mixture of 2.5% methanol in dichloromethane. Relevant fractions were combined and evaporated to give the title product (203 mg).

Source