Potassium Carbonate → HCID 11677428, compound

HRID 1994498Notes

Reaction equation

HRID 1994498 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1I)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([CH:34]([CH3:36])[CH3:35])=[CH:30][C:29]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>CC(C)=O.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[CH2:14][C:15]1[CH:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[CH:18]=[CH:17][C:16]=1[C:33]1[CH:32]=[C:31]([CH:34]([CH3:36])[CH3:35])[CH:30]=[CH:29][C:28]=1[O:27][CH3:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 45891905-Isopropyl-2-methoxyphenylboronic acidHCID 66716634HCID 66716634, compound

Product 1

HCID 11677428HCID 11677428, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

A stirred suspension of (4S)-4-benzyl-3-[2-iodo-5-(trifluoromethyl)benzyl]1,3-oxazolidin-2-one (63 mg, 0.137 mmol), 2-methoxy-5-isopropylphenyl boronic acid (52 mg, 0.274 mmol), K2CO3 (47 mg, 0.34 mmol) and Pd(OAc)2 (9.2 mg, 0.0137 mmol) in acetone:H2O (5:1) (6 mL) was heated at reflux for 1 h. The reaction mixture was concentrated in vacuo, diluted with H2O (15 mL) and extracted with EtOAC (3×30 mL). The combined organic extracts were washed with brine (30 mL), dried (MgSO4), filtered and concentrated. The crude product was purified by silica-gel flash chromatography (0-20% EtOAc in hexanes gradient) to (4S)-4-benzyl-3-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-1,3-oxazolidin-2-one. Rf=0.35 (15% EtOAc/hexanes). LCMS 484 (M+1)+. 1H NMR (CDCl3, 500 MHz) (atropisomers present; doubling of some peaks observed in 1H NMR) δ 7.72 (br s 1H), 7.65 (br s, 1H), 7.42 (m, 1H), 7.32-7.22 (m, 3H), 7.08 (d, J=2.3 Hz, 1H), 6.90-6.84 (m, 3H), 4.80 (d, J=15.8 Hz, 1H), 4.35 (d, J=15.8 Hz), 4.28 (t, J=8.7 Hz, 1H), 3.96-3.92 (m, 3H), 3.78 (s, 3H), 3.62-3.52 (m, 1H), 2.94-2.86 (m, 1H), 2.82 (dd, J=9.4, 3.9 Hz, 1H), 2.42 (dd, J=9.6, 3.9 Hz), 1.26 (s, 3H), 1.10 (s, 3H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. additiondiluted with H2O (15 mL)
  5. extractionextracted with EtOAC (3×30 mL)
  6. washThe combined organic extracts were washed with brine (30 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by silica-gel flash chromatography (0-20% EtOAc in hexanes gradient) to (4S)-4-benzyl-3-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-1,3-oxazolidin-2-one

Sources & evidence

ORD record
ord-1b73ae0e9cd34702852f46034f8f8914
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

Loading…