1,2-Dimethoxyethane → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(6-isopropenylpyridin-2-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1994553Notes

Reaction equation

HRID 1994553 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH3:10])=[CH2:9])[N:3]=1.[F:11][C:12]([F:51])([F:50])[C:13]1[CH:14]=[C:15]([C@H:23]2[O:27][C:26](=[O:28])[N:25]([CH2:29][C:30]3[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[CH:32][C:31]=3B3OC(C)(C)C(C)(C)O3)[C@H:24]2[CH3:49])[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1.COCCOC.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO>[F:51][C:12]([F:11])([F:50])[C:13]1[CH:14]=[C:15]([C@H:23]2[O:27][C:26](=[O:28])[N:25]([CH2:29][C:30]3[CH:35]=[C:34]([C:36]([F:37])([F:38])[F:39])[CH:33]=[CH:32][C:31]=3[C:2]3[CH:7]=[CH:6][CH:5]=[C:4]([C:8]([CH3:10])=[CH2:9])[N:3]=3)[C@H:24]2[CH3:49])[CH:16]=[C:17]([C:19]([F:20])([F:22])[F:21])[CH:18]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 221642832-Bromo-6-(prop-1-en-2-yl)pyridineHCID 57704783(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one

Product 1

HCID 11721263(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(6-isopropenylpyridin-2-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

In a tube were placed 2-bromo-6-isopropenylpyridine (17.5 mg, 0.0878 mmol), (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-3-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)benzyl]-1,3-oxazolidin-2-one (26.2 mg, 0.0439 mmol), DME (190 μL), EtOH (62 μL), and 1M aqueous Na2CO3 (100 μL, 0.1 mmol). The mixture was degassed with N2. Next, Pd(PPh3)4 (9 mg, 7.8×10−3 mmol) was added and the mixture was degassed again with N2. The tube was sealed and heated at 100° C. for 2 hours. The reaction was then cooled to room temperature, diluted with EtOAc (50 mL), and 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 (5 to 25% EtOAc/hexanes) afforded (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(6-isopropenylpyridin-2-yl)-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one. Rf=0.15 (15% EtOAc/hexanes). LCMS=589.1 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.81-7.85 (m, 2H), 7.74 (s, 1H), 7.69-7.69 (m, 3H), 7.58 (d, J=8.0 Hz, 1H), 7.53 (d, J=7.7 Hz, 1H), 7.34 (d, J=7.6 Hz, 1H), 5.94 (s, 1H), 5.48 (d, J=7.7 Hz, 1H), 5.36 (s, 1H), 5.06 (d, J=16.0 Hz, 1H), 4.47 (d, J=16.1 Hz, 1H), 3.91 (m, 1H), 2.23 (s, 3H), 0.50 (d, J=6.6 Hz, 3H).

Workup

  1. customIn a tube were placed
  2. customThe mixture was degassed with N2
  3. customthe mixture was degassed again with N2
  4. customThe tube was sealed
  5. temperatureThe reaction was then cooled to room temperature
  6. additiondiluted with EtOAc (50 mL)
  7. washwashed with water and brine (15 mL each)
  8. dry with materialThe organic layer was dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification of the residue by flash chromatography on silica gel (5 to 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-26920e3d284d47369d697a1737d08069
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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