Cesium carbonate → 5-(Chloromethyl)-3-(5-chloropyridin-2-yl)-1,3-oxazolidin-2-one

HRID 2066801Notes

Reaction equation

HRID 2066801 reaction equation
[Cl:1][CH2:2][CH:3]1[O:7][C:6](=[O:8])[NH:5][CH2:4]1.Br[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>O1CCOCC1>[Cl:1][CH2:2][CH:3]1[O:7][C:6](=[O:8])[N:5]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][N:11]=2)[CH2:4]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 908155-Chloromethyloxazolidin-2-oneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 8170982-Bromo-5-chloropyridine

Product 1

HCID 594099115-(Chloromethyl)-3-(5-chloropyridin-2-yl)-1,3-oxazolidin-2-oneYield 83%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 5-(chloromethyl)-1,3-oxazolidin-2-one (136 mg), 2-bromo-5-chloropyridine (192 mg), cesium carbonate (489 mg), bispalladium tribenzylideneacetone (137 mg) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (260 mg) in 1 ml of dioxane was stirred at 85° C. for 12 h. The sample was then cooled to room temperature, and filtered through a plug of silica gel (5×10 ml) eluting with ethyl acetate (50 ml). The eluent was concentrated in vacuo to provide a clear reddish-brown liquid, which was purified via column chromatography on a Biotage Horizon 40M column eluting with 0% ethyl acetate in hexanes (1 column volume), followed by a gradient to 100% ethyl acetate in hexanes (over 10 column volumes), and held at 100% ethyl acetate for 4 column volumes to provide the title compound (204 mg, 83%). Mass spectrum (ESI) 249.0 (M+2). 1H NMR (500 MHz, CDCl3): δ 8.28 (d, J=2.5 Hz, 1H), 8.20 (d, J=8.9 Hz, 1H), 7.68 (dd, J=9.0, 2.6 Hz, 1H), 4.90 (m, 1H), 4.35 (dd, J=8.9, 11.0 Hz, 1H), 4.17 (dd, J=5.7, 10.8 Hz, 1H), 3.78 (m, 2H).

Workup

  1. temperatureThe sample was then cooled to room temperature
  2. filtrationfiltered through a plug of silica gel (5×10 ml)
  3. washeluting with ethyl acetate (50 ml)
  4. concentrationThe eluent was concentrated in vacuo
  5. customto provide a clear reddish-brown liquid, which
  6. customwas purified via column chromatography on a Biotage Horizon 40M column
  7. washeluting with 0% ethyl acetate in hexanes (1 column volume)

Sources & evidence

ORD record
ord-bcbd0dfb77b04ac39c13116a98dc40a8
Source dataset
uspto-grants-2012_10
Patent number
US08293721B2

Reaction notes

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