Sodium hydride → (4s,5s)-3-{[4'-Fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-5-(4-methyl-1,3-thiazol-2-yl)-1,3-oxazolidin-2-one

HRID 1028617Notes

Reaction equation

HRID 1028617 reaction equation
[H-].[Na+].[CH3:3][C@H:4]1[C@@H:8]([C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)[O:7][C:6](=[O:15])[NH:5]1.Br[CH2:17][C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1[C:28]1[CH:33]=[C:32]([CH:34]([CH3:36])[CH3:35])[C:31]([F:37])=[CH:30][C:29]=1[O:38][CH3:39].[NH4+].[Cl-]>C1COCC1>[F:37][C:31]1[C:32]([CH:34]([CH3:36])[CH3:35])=[CH:33][C:28]([C:19]2[CH:20]=[CH:21][C:22]([C:24]([F:26])([F:27])[F:25])=[CH:23][C:18]=2[CH2:17][N:5]2[C@@H:4]([CH3:3])[C@@H:8]([C:9]3[S:10][CH:11]=[C:12]([CH3:14])[N:13]=3)[O:7][C:6]2=[O:15])=[C:29]([O:38][CH3:39])[CH:30]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 533638292'-(Bromomethyl)-4-fluoro-5-isopropyl-2-methoxy-4'-(trifluoromethyl)biphenylHCID 66716948(4S,5S)-4-methyl-5-(4-methyl-1,3-thiazol-2-yl)-1,3-oxazolidin-2-one

Product 1

HCID 11678057(4s,5s)-3-{[4'-Fluoro-5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-5-(4-methyl-1,3-thiazol-2-yl)-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Sodium hydride (60% dispersion in mineral oil, 8.1 mg, 0.202 mmol) was added to a stirred solution of (4S,5S)-4-methyl-5-(4-methyl-1,3-thiazol-2-yl)-1,3-oxazolidin-2-one (33.4 mg, 0.168 mmol) in dry THF (1 mL) at room temperature under N2. The reaction was stirred for 15 min then a solution of 2′-(bromomethyl)-4-fluoro-5-isopropyl-2-methoxy-4′-(trifluoromethyl)biphenyl (81.0 mg, 0.202 mmol) in dry THF (2 mL) was added by cannula. The reaction was stirred at room temperature overnight. Saturated NH4Cl (10 mL) was added and the mixture was extracted with EtOAc (3×20 mL). The combined extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 25×160 mm, 0-70% EtOAc in hexanes gradient) and chiral HPLC (IA column, 20×250 mm, 5% i-PrOH in heptane) to afford (4S,5S)-3-{[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-5-(4-methyl-1,3-thiazol-2-yl)-1,3-oxazolidin-2-one. Rf=0.18 (20% EtOAc in hexanes). LCMS calc.=523.2; found=523.1 (M+1)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers) δ 7.68 (s, 0.5H), 7.63 (s, 0.5H), 7.59 (d, J=8.0 Hz, 1H), 7.32 (d, J=7.9 Hz, 1H), 6.99 (d, J=8.5 Hz, 0.5H), 6.95 (d, J=8.5 Hz, 0.5H), 6.88 (s, 1H), 6.68 (d, J=5.0 Hz, 0.5H), 6.66 (d, J=4.9 Hz, 0.5H), 5.70 (d, J=8.3 Hz, 0.5H), 5.55 (d, J=8.2 Hz, 0.5H), 4.72 (d, J=15.9 Hz, 0.5H), 4.64 (d, J=15.9 Hz, 0.5H), 4.20 (d, J=15.9 Hz, 0.5H), 3.95 (d, J=15.9 Hz, 0.5H), 3.91-3.83 (m, 1H), 3.75 (s, 1.5H), 3.74 (s, 1.5H), 3.23-3.15 (m, 1H), 2.40 (s, 3H), 1.26-1.18 (m, 6H), 0.65 (d, J=6.5 Hz, 1.5H), 0.55 (d, J=6.5 Hz, 1.5H).

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. extractionthe mixture was extracted with EtOAc (3×20 mL)
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThis was purified by flash chromatography (Si, 25×160 mm, 0-70% EtOAc in hexanes gradient) and chiral HPLC (IA column, 20×250 mm, 5% i-PrOH in heptane)

Sources & evidence

ORD record
ord-752045e1fe364735ae600db13bfc4c4f
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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