Nitrogen → HCID 11520123, compound

HRID 1994550Notes

Reaction equation

HRID 1994550 reaction equation
N[C:2]1[CH:3]=[CH:4][C:5]([O:40][CH3:41])=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=2[CH2:18][N:19]2[C@@H:23]([CH3:24])[C@@H:22]([C:25]3[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=3)[O:21][C:20]2=[O:39])[CH:7]=1.N#N.[CH3:44][S:45]SC.N(OC(C)(C)C)=O>C(Cl)(Cl)Cl>[F:36][C:35]([F:38])([F:37])[C:27]1[CH:26]=[C:25]([C@H:22]2[O:21][C:20](=[O:39])[N:19]([CH2:18][C:9]3[CH:10]=[C:11]([C:14]([F:15])([F:17])[F:16])[CH:12]=[CH:13][C:8]=3[C:6]3[CH:7]=[C:2]([S:45][CH3:44])[CH:3]=[CH:4][C:5]=3[O:40][CH3:41])[C@H:23]2[CH3:24])[CH:30]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:28]=1

Participants

6

Reactant 4

HCID 947NitrogenHCID 10906Tert-Butyl nitriteHCID 12232Dimethyl DisulfideHCID 11592394HCID 11592394, compound

Product 1

HCID 11520123HCID 11520123, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of (4S,5R)-3-{[5′-amino-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (Example 123) (40 mg, 0.0676 mmol) in CHCl3 (1 mL) that had been degassed with N2 was added methyl disulfide (10 μL, 0.101 mmol) and t-butyl nitrite (16 μL, 0.135 mmol). The reaction was stirred at room temperature for 30 minutes and then heated to reflux for 2 hours. The reaction was then cooled to room temperature and diluted with hexanes (3 mL). The solution was loaded directly onto a silica gel column and eluted with 25% EtOAc/hexanes. Fractions containing the desired product were combined and repurified by silica gel chromatography with 5 to 25% EtOAc/hexanes to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[2′-methoxy-5′-(methylthio)-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one. Rf=0.52 (40% EtOAc/hexanes). LCMS=624.1 (M+1)+. 1H NMR (CDCl3, 600 MHz, rotamers present) δ 6.94-7.85 (m, 9H), 5.58 (d, J=8.1 Hz) 5.25 (d, J=7.8 Hz), 4.94 (d, J=15.8 Hz), 4.85 (d, J=15.7 Hz), 3.65-4.12 (m, 5H), 2.47 (s), 2.44 (s), 0.54 (d, J=6.6 Hz), 0.40 (d, J=6.6 Hz).

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 hours
  3. temperatureThe reaction was then cooled to room temperature
  4. washeluted with 25% EtOAc/hexanes
  5. additionFractions containing the desired product
  6. customrepurified by silica gel chromatography with 5 to 25% EtOAc/hexanes

Sources & evidence

ORD record
ord-48ee008188bf4ebfbb794e66f57b9659
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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