Methyl iodide → HCID 178471798, compound

HRID 505313Notes

Reaction equation

HRID 505313 reaction equation
[F:1][C:2]([F:48])([F:47])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:30])([F:29])[F:28])[CH:23]=[CH:22][C:21]=3[NH:31][C:32]([C@H:34]3[CH2:39][CH2:38][C@H:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:36][CH2:35]3)=[O:33])[C@H:14]2[CH3:46])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].I[CH3:52]>C1COCC1>[F:12][C:9]([F:11])([F:10])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:30])([F:28])[F:29])[CH:23]=[CH:22][C:21]=3[N:31]([CH3:52])[C:32]([C@H:34]3[CH2:39][CH2:38][C@H:37]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:36][CH2:35]3)=[O:33])[C@H:14]2[CH3:46])[CH:4]=[C:3]([C:2]([F:1])([F:47])[F:48])[CH:8]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 178471797HCID 178471797, compound

Product 1

HCID 178471798HCID 178471798, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of ethyl [trans-4-({[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl]amino}carbonyl)cyclohexyl]acetate (500 mg; 0.716 mmol) in anhydrous THF (10 mL) was cooled to 0° C. and treated with sodium hydride (60% in oil; 31.5 mg; 0.788 mmol). The resultant mixture was stirred at 0° C. for 30 min prior to addition of iodomethane (58 μL; 0.931 mmol). The reaction was stirred at room temperature for 14 h and quenched with H2O. The reaction was partitioned between EtOAc (50 mL) and H2O (50 mL) and the aqueous layer was extracted with EtOAc (3×50 mL). The combined extracts were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography, eluting with EtOAc/hexanes, and by chiral HPLC (chiralPak IA column, 10% iPrOH/heptane) to afford ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](methyl)amino]carbonyl}cyclohexyl)acetate as a clear oil. LCMS=713.0 (M+1)+. 1H NMR (CDCl3, 500 MHz, mixture of atropisomers): δ 7.92 (s, 1 H), 7.80 (s, 1 H), 7.73 (s, 1H), 7.29-7.20 (m, 2 H), 7.17-7.15 (m, 1 H), 5.66 (d, J=8.3 Hz, 1 H), 4.95 (d, J=14.8 Hz, 1 H), 4.22 (d, J=16.7 Hz, 1 H), 4.14-4.06 (m, 2 H), 3.897 (d, J=14.7 Hz, 1 H), 3.39 (s, 3 H), 2.70-2.63 (m, 1 H), 2.22-2.18 (m, 1 H), 2.10-2.07 (m, 1 H), 2.00-1.52 (m, 8 H), 1.27-1.19 (m, 3 H), 1.16-1.08 (m, 1 H), 0.76-0.68 (m, 3 H).

Workup

  1. customquenched with H2O
  2. customThe reaction was partitioned between EtOAc (50 mL) and H2O (50 mL)
  3. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
  4. washThe combined extracts were washed with brine (50 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash silica gel chromatography
  9. washeluting with EtOAc/hexanes

Sources & evidence

ORD record
ord-aecbe04755984878a0cff6a5b94baadc
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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