Water → HCID 24969814, compound

HRID 604650Notes

Reaction equation

HRID 604650 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:29](I)=[CH:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][C:26]=4[N+:31]([O-:33])=[O:32])[CH:21]=3)[C@H:14]2[CH3:34])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[F:37][C:38]1[C:43]([CH:44]([CH3:46])[CH3:45])=[CH:42][C:41](B(O)O)=[C:40]([O:50][CH3:51])[CH:39]=1.O>C(=O)([O-])[O-].[K+].[K+].C1COCC1>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:29]([C:41]4[CH:42]=[C:43]([CH:44]([CH3:46])[CH3:45])[C:38]([F:37])=[CH:39][C:40]=4[O:50][CH3:51])=[CH:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][C:26]=4[N+:31]([O-:33])=[O:32])[CH:21]=3)[C@H:14]2[CH3:34])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 962WaterHCID 53363739(4-Fluoro-5-isopropyl-2-methoxyphenyl)boronic acidHCID 86627630HCID 86627630, compound

Product 1

HCID 24969814HCID 24969814, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 11430Potassium CarbonateSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-iodo-5-nitro-2-naphthyl)methyl]-4-methyl-1,3-oxazolidin-2-one (34.0 mg, 0.0545 mmol), (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (23.1 mg, 0.0109 mmol), and 1,1′-bis(di-t-butylphosphinoferrocene)palladium dichloride (3.5 mg, 0.00545 mmol) in 1N aqueous potassium carbonate (2 mL) and THF (2 mL) was heated at 85° C. in a sealed tube for 2 h. 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, 0-30% EtOAc in hexanes gradient) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-5-nitro-2-naphthyl]methyl}-4-methyl-1,3-oxazolidin-2-one. Rf=0.23 (20% EtOAc/hexanes). LCMS calc.=665.2; found=664.9 (M+1)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers): δ 8.46 (s, 1H); 8.26 (d, J=7.5 Hz, 1H); 8.17 (t, J=9.0 Hz, 1H); 8.07 (s, 0.5H); 7.95 (s, 0.5H); 7.85 (s, 1H); 7.69 (s, 2H); 7.58 (t, J=7.9 Hz, 1H); 7.14 (d, J=8.4 Hz, 0.5H); 7.10 (d, J=8.4 Hz, 0.5H); 6.72 (d, J=12.0 Hz, 0.5H); 6.71 (d, J=12.0 Hz, 0.5H); 5.57 (d, J=8.1 Hz, 0.5H); 5.44 (d, J=8.0 Hz, 0.5H); 4.97 (d, J=15.9 Hz, 0.5H); 4.93 (d, J=15.9 Hz, 0.5H); 4.29 (d, J=15.9 Hz, 0.5H); 4.03 (d, J=15.8 Hz, 0.5H); 3.91-3.83 (m, 0.5H); 3.77 (m, 3.5H); 3.26-3.18 (m, 1H); 1.28-1.24 (m, 4.5H); 1.20 (d, J=6.9 Hz, 1.5H); 0.58 (d, J=6.5 Hz, 1.5H); 0.40 (d, J=6.6 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, 0-30% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-42bb0f863748427a9b82805104baa620
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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