Sodium Carbonate → (4s,5r)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 604648Notes

Reaction equation

HRID 604648 reaction equation
FC(F)(F)S(O[C:7]1[C:16]([CH2:17][N:18]2[C@@H:22]([CH3:23])[C@@H:21]([C:24]3[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[C:26]([C:34]([F:37])([F:36])[F:35])[CH:25]=3)[O:20][C:19]2=[O:38])=[CH:15][C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[CH:8]=1)(=O)=O.[F:41][C:42]1[C:47]([CH:48]([CH3:50])[CH3:49])=[CH:46][C:45](B(O)O)=[C:44]([O:54][CH3:55])[CH:43]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC=CC=1.CCO.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:37][C:34]([F:35])([F:36])[C:26]1[CH:25]=[C:24]([C@H:21]2[O:20][C:19](=[O:38])[N:18]([CH2:17][C:16]3[C:7]([C:45]4[CH:46]=[C:47]([CH:48]([CH3:50])[CH3:49])[C:42]([F:41])=[CH:43][C:44]=4[O:54][CH3:55])=[CH:8][C:9]4[CH2:10][CH2:11][CH2:12][CH2:13][C:14]=4[CH:15]=3)[C@H:22]2[CH3:23])[CH:29]=[C:28]([C:30]([F:31])([F:32])[F:33])[CH:27]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 53363739(4-Fluoro-5-isopropyl-2-methoxyphenyl)boronic acidHCID 866276293-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate

Product 1

HCID 24969813(4s,5r)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 241BenzeneSolventHCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
95 °C

Procedure

A mixture of 3-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-5,6,7,8-tetrahydronaphthalen-2-yl trifluoromethanesulfonate (12.4 mg, 0.0204 mmol), (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (13.0 mg, 0.0614 mmol), and tetrakis(triphenylphosphine)palladium (0) (2.8 mg, 0.00246 mmol), sodium carbonate (18.2 mg, 0.172 mmol) in benzene (1.4 mL), EtOH (0.2 mL) and water (0.6 mL) was heated at 95° C. in a sealed tube overnight. The reaction mixture was cooled to room temperature and water (10 mL) was added. The mixture was extracted with EtOAc (3×20 mL) and the combined organic extracts were dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 12×160 mm, 0-20% EtOAc in hexanes gradient) and chiral HPLC (IA column, 20×250 mm, 3% i-PrOH in heptane) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-5,6,7,8-tetrahydronaphthalen-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. Rf=0.49 (20% EtOAc/hexanes). LCMS calc.=624.2; found=624.2 (M+1)+. 1H NMR (600 MHz, CDCl3, 1:1 mixture of atropisomers): δ 7.83 (s, 1H); 7.67 (s, 1H); 7.65 (s, 1H); 7.17 (s, 0.5H); 7.06 (s, 0.5H); 7.01 (d, J=8.6 Hz, 0.5H); 6.98 (d, J=8.6 Hz, 0.5H); 6.94 (s, 0.5H); 6.91 (s, 0.5H); 6.65 (d, J=9.6 Hz, 0.5H); 6.63 (d, J=9.5 Hz, 0.5H); 5.52 (d, J=8.2 Hz, 0.5H); 5.23 (d, J=8.0 Hz, 0.5H); 4.85 (d, J=15.2 Hz, 0.5H); 4.79 (d, J=15.3 Hz, 0.5H); 3.95 (d, J=15.3 Hz, 0.5H); 3.77-3.71 (m, 4.5H); 3.22-3.14 (m, 1H); 2.84-2.77 (m, 4H); 1.86-1.80 (m, 4H); 1.27-1.21 (m, 4.5H); 1.15 (d, J=7.0 Hz, 1.5H); 0.50 (d, J=6.5 Hz, 1.5H); 0.28 (d, J=6.5 Hz, 1.5H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe mixture was extracted with EtOAc (3×20 mL)
  3. dry with materialthe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThis was purified by flash chromatography (Si, 12×160 mm, 0-20% EtOAc in hexanes gradient) and chiral HPLC (IA column, 20×250 mm, 3% i-PrOH in heptane)

Sources & evidence

ORD record
ord-df670cd7114949dba2dcc2918c9a9cfe
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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