Propargyl bromide → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-prop-2-yn-1-yl-1,3-oxazolidin-2-one

HRID 604653Notes

Reaction equation

HRID 604653 reaction equation
[H-].[Na+].[F:3][C:4]([F:23])([F:22])[C:5]1[CH:6]=[C:7]([C@H:15]2[O:19][C:18](=[O:20])[NH:17][C@H:16]2[CH3:21])[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1.[CH2:24](Br)[C:25]#[CH:26].[NH4+].[Cl-]>C1COCC1>[F:23][C:4]([F:3])([F:22])[C:5]1[CH:6]=[C:7]([C@H:15]2[O:19][C:18](=[O:20])[N:17]([CH2:26][C:25]#[CH:24])[C@H:16]2[CH3:21])[CH:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=1

Participants

6

Reactant 4

HCID 7842Propargyl bromideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one

Product 1

HCID 86627632(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-prop-2-yn-1-yl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Sodium hydride (192 mg, 60% dispersion in mineral oil, 4.79 mmol) was added to a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (1.00 g, 3.19 mmol) in dry THF (30 mL) at room temperature under N2. After stirring for 30 min at room temperature, propargyl bromide (80 wt % solution in toluene, 712 μL, 570 mg, 4.17 mmol) was added. The reaction mixture was stirred overnight at room temperature. Saturated NH4Cl (20 mL) was added and the mixture was extracted with EtOAc (3×20 mL). The combined extracts were dried (MgSO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 40×160 mm, 0-40% EtOAc in hexanes gradient) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-prop-2-yn-1-yl-1,3-oxazolidin-2-one. Rf=0.31 (20% EtOAc/hexanes). LCMS calc.=352.1; found=352.1 (M+1)+. 1H NMR (600 MHz, CDCl3): δ 7.88 (s, 1H); 7.76 (s, 2H); 5-74 (d, J=8.2 Hz, 1H); 4.454-39 (m, 2H); 3.81 (dd, J=2.5, 17.8 Hz, 1H); 2.33 (t, J=2.5 Hz, 1H); 0.84 (d, J=6.6 Hz, 4H).

Workup

  1. stirringThe reaction mixture was stirred overnight at room temperature
  2. extractionthe mixture was extracted with EtOAc (3×20 mL)
  3. dry with materialThe combined extracts were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThis was purified by flash chromatography (Si, 40×160 mm, 0-40% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-d9f003a8daec4bc5b578e5966e173f27
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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