Reaktion #85659

ord-6a98da00d7f44055a93b117d3b0bcd70

Reaktionsgleichung

C[C@@H](C(F)F)[C@H]1COC(=O)N1
(S)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one
Fc1cnc(Cl)nc1Cl
2,4-dichloro-5-fluoropyrimidine
[H-].[Na+]
sodium hydride
[H-].[Na+]
sodium hydride
[H-].[Na+]
sodium hydride
C[C@@H](C(F)F)[C@H]1COC(=O)N1c1nc(Cl)ncc1F
(S)-3-(2-chloro-5-fluoropyrimidin-4-yl)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one
Ausbeute 65.7%

Reaktionsbedingungen

Temperatur
5°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.STIRRINGstirred for 5 min
  2. 2
    SonstigeThe aqueous layer was separated
  3. 3
    Extraktionextracted with ethylacetate (25 mL)
  4. 4
    WaschenThe combined organic layers were washed with brine (30 mL)
  5. 5
    Trocknendried over sodium sulfate
  6. 6
    Filtrationfiltered off
  7. 7
    Einengenconcentrated under reduced pressure
  8. 8
    SonstigeThe residue was purified by column chromatography [SiO2, 12 g, EtOAc/heptane]

Vorschrift

To a solution of (S)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one (114 mg, 069 mmol) and 2,4-dichloro-5-fluoropyrimidine (115 mg, 0.690 mmol) in DMF (2.26 mL) was added sodium hydride (60% wt.; 35.9 mg) in three portions at <0° C. (sodium chloride/ice). After the first portion of sodium hydride the mixture was stirred for ˜5 min. The remaining two portions of sodium hydride were added over ˜5 min and stirring was continued for 30 min. The mixture was diluted with ethylacetate (10 mL), stirred for 5 min and further slowly diluted with brine/water (1/1; 10 mL). The mixture was allowed to warm to 5° C. and poured into a mixture of brine/water (1/1; 10 mL) and ethylacetate (10 mL). The aqueous layer was separated and extracted with ethylacetate (25 mL). The combined organic layers were washed with brine (30 mL), dried over sodium sulfate, filtered off and concentrated under reduced pressure. The residue was purified by column chromatography [SiO2, 12 g, EtOAc/heptane] to provide (S)-3-(2-chloro-5-fluoropyrimidin-4-yl)-4-((R)-1,1-difluoropropan-2-yl)oxazolidin-2-one (134 mg) as a white solid. MS m/z 296.1 (M+H)+; Rt-0.75 min. 1H NMR (400 Mhz, CD3OD) δ ppm 8.69 (d, J=2.6 Hz, 1H), 5.99 (q, J=1.0 Hz, 1H), 5.17 (ddd, J=3.5, 7.4, 8.6 Hz, 1H), 4.69-4.50 (m, 2H), 2.88-2.70 (m, 1H), 1.04 (d, J=7.1 Hz, 3H).

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US09434719B2uspto-grants-2016_09