Chloroform → HCID 57576243, compound

HRID 604652Notes

Reaction equation

HRID 604652 reaction equation
N(OC(C)(C)C)=O.N[C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[C:12]([C:41]1[CH:46]=[C:45]([CH:47]([CH3:49])[CH3:48])[C:44]([F:50])=[CH:43][C:42]=1[O:51][CH3:52])[C:13]([CH2:19][N:20]1[C@@H:24]([CH3:25])[C@@H:23]([C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[O:22][C:21]1=[O:40])=[CH:14]2.C(Cl)(Cl)Cl.C(I)[I:58]>>[F:34][C:32]([F:35])([F:33])[C:30]1[CH:31]=[C:26]([C@H:23]2[O:22][C:21](=[O:40])[N:20]([CH2:19][C:13]3[C:12]([C:41]4[CH:46]=[C:45]([CH:47]([CH3:49])[CH3:48])[C:44]([F:50])=[CH:43][C:42]=4[O:51][CH3:52])=[CH:11][C:10]4[C:15](=[CH:16][CH:17]=[CH:18][C:9]=4[I:58])[CH:14]=3)[C@H:24]2[CH3:25])[CH:27]=[C:28]([C:36]([F:39])([F:37])[F:38])[CH:29]=1

Participants

5

Reactant 4

HCID 6212ChloroformHCID 6346DiiodomethaneHCID 10906Tert-Butyl nitriteHCID 24969815HCID 24969815, compound

Product 1

HCID 57576243HCID 57576243, compound

Conditions

Temperature
80 °C

Procedure

t-Butyl nitrite (90%, 6.5 mg, 8.3 μL, 0.0627 mmol) was added to a suspension of (4S,5R)-3-{[5-amino-3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-2-naphthyl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (19.9 mg, 0.0314 mmol) in CH2I2 (1 mL). Dry CHCl3 (0.5 mL) was added to dissolve the precipitate formed. The solution was heated at 80° C. for 5 h. The reaction mixture was concentrated in vacuo and the resulting slurry was purified by flash chromatography (Si, 12×160 mm, 0-20% EtOAc in hexanes gradient) to afford (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[3-(4-fluoro-5-isopropyl-2-methoxyphenyl)-5-iodo-2-naphthyl]methyl}-4-methyl-1,3-oxazolidin-2-one. Rf=0.47 (20% EtOAc/hexanes). LCMS calc.=746.1; found 745.8 (M+1)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers): δ 8.11 (d, J=7.2 Hz, 1H); 7.92 (d, J=4.7 Hz, 1H); 7.88-7.85 (m, 1.5H); 7.84 (s, 1H); 7.75 (s, 0.5H); 7.67 (s, 2H); 7.22 (t, J=7.7 Hz, 1H); 7.16 (d, J=8.5 Hz, 0.5H); 7.12 (d, J=8.5 Hz, 0.5H); 6.76-6.70 (m, 1H); 5.54 (d, J=8.1 Hz, 0.5H); 5.34 (d, J=8.0 Hz, 0.5H); 5.01 (d, J=15.7 Hz, 0.5H); 5.00 (d, J=15.7 Hz, 0.5H); 4.22 (d, J=15.7 Hz, 0.5H); 3.98 (d, J=15.7 Hz, 0.5H); 3.81-3.72 (m, 4H); 3.28-3.20 (m, 1H); 1.32-1.24 (m, 4.5H); 1.21 (d, J=6.9 Hz, 1.5H); 0.57 (d, J=6.5 Hz, 1.5H); 0.37 (d, J=6.5 Hz, 1.5H).

Workup

  1. dissolutionto dissolve the precipitate
  2. customformed
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthe resulting slurry was purified by flash chromatography (Si, 12×160 mm, 0-20% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-987b9f47b9f243a4ba98ba4c5b918ea5
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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