2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)benzaldehyde → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(1-hydroxypropyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

HRID 505260Notes

Reaction equation

HRID 505260 reaction equation
[F:1][C:2]([F:34])([F:33])[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:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:21]=3[CH:22]=[O:23])[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:35][CH2:36][Mg+].[Br-]>C(OCC)C>[F:34][C:2]([F:1])([F:33])[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:27]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:25]=[CH:24][C:21]=3[CH:22]([OH:23])[CH2:35][CH3:36])[C@H:14]2[CH3:32])[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=1

Participants

4

Reactant 2

HCID 576178812-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)benzaldehydeHCID 178461630HCID 178461630, compound2×

Product 1

HCID 86628753(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(1-hydroxypropyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a −78° C. solution of 2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethyl)benzaldehyde (230 mg, 0.461 mmol) in diethyl ether (5 mL) was added a solution of EtMgBr (230 μL, 0.691 mmol). The solution was stirred for 5 minutes, followed by a second addition of EtMgBr solution (230 μL, 0.691 mmol). After 5 minutes, the reaction was quenched with saturated NH4Cl solution (5 mL), diluted with EtOAc (60 mL), and washed with brine (30 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography on silica gel (10 to 35% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(1-hydroxypropyl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.14 (25% EtOAc/hexanes). LCMS=512.1 (M+1−18)+. 1H NMR (CDCl3, 500 MHz, diastereomers present) δ 7.89-7.45 (m, 6H), 5.69-6.65 (m, 1H), 5.04-4.91 (m, 1H), 4.27-4.18 (m, 1H), 4.03-3.93 (m, 1H), 2.87 (m, 1H), 1.89-1.66 (m, 2H), 1.00-0.93 (m, 3H), 0.79-0.75 (m, 3H).

Workup

  1. waitAfter 5 minutes
  2. customthe reaction was quenched with saturated NH4Cl solution (5 mL)
  3. additiondiluted with EtOAc (60 mL)
  4. washwashed with brine (30 mL)
  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 (10 to 35% EtOAc/hexanes)

Sources & evidence

ORD record
ord-5039d114c97c484386d79efc4243450b
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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