Sodium bis(trimethylsilyl)amide → HCID 59135105, compound

HRID 1028594Notes

Reaction equation

HRID 1028594 reaction equation
[F:1][C:2]([F:40])([F:39])[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]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[S:31][C:32]([CH:35]([OH:37])[CH3:36])=[CH:33][N:34]=3)[C@H:14]2[CH3:38])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:41][Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1.CI>[F:40][C:2]([F:1])([F:39])[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]([C:26]([F:28])([F:29])[F:27])[CH:23]=[CH:22][C:21]=3[C:30]3[S:31][C:32]([CH:35]([O:37][CH3:41])[CH3:36])=[CH:33][N:34]=3)[C@H:14]2[CH3:38])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 2

HCID 2724254Sodium bis(trimethylsilyl)amide2×HCID 86603423HCID 86603423, compound

Product 1

HCID 59135105HCID 59135105, compound

Reagents, catalysts & solvents 2

HCID 6328Methyl iodideCatalyst2×HCID 8028TetrahydrofuranSolvent3×

Procedure

To a 0° C. solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[5-(1-hydroxyethyl)-1,3-thiazol-2-yl]-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one (Example 154) (13.2 mg, 0.0221 mmol) in THF (1 mL) was added NaHMDS (26.5 μL of a 1M solution in THF, 0.0265 mmol) followed by MeI (1 drop). After 1.5 hours, additional NaHMDS (15 μL of a 1M solution in THF, 0.015 mmol) and MeI (1 drop) were added to the reaction. The reaction was warmed to room temperature for 20 minutes and then quenched by pouring into saturated NH4Cl (10 mL). The mixture was extracted with EtOAc (35 mL) and the organic layer was washed with water and brine (15 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (15 to 75% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-[5-(1-methoxyethyl)-1,3-thiazol-2-yl]-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.37 (40% EtOAc/hexanes). LCMS=613.0 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.87 (s, 1H), 7.74-7.82 (m, 5H), 7.67 (d, J=8.0 Hz, 1H), 6.63-5.66 (m, 1H), 5.08-5.14 (m, 1H), 4.83-4.88 (m, 1H), 4.64-4.68 (m, 1H), 4.01-4.08 (m, 1H), 3.34 (m, 3H), 1.60 (d, J=6.4 Hz, 3H), 0.69 (d, J=6.7 Hz, 3H).

Workup

  1. customquenched
  2. additionby pouring into saturated NH4Cl (10 mL)
  3. extractionThe mixture was extracted with EtOAc (35 mL)
  4. washthe organic layer was washed with water and brine (15 mL each)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue by flash chromatography on silica gel (15 to 75% EtOAc/hexanes)

Sources & evidence

ORD record
ord-b9b5e53ead0a4157a9077623108ad2d1
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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