Toluene → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5'-bromo-4-fluoro-2'-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 607062Notes

Reaction equation

HRID 607062 reaction equation
[F:1][C:2]([F:30])([F:29])[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]([F:26])[CH:23]=[CH:22][C:21]=3Br)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Br:31][C:32]1[CH:33]=[CH:34][C:35]([O:41][CH3:42])=[C:36](B(O)O)[CH:37]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>[Cl-].[Na+].O.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.C(O)C>[F:10][C:9]([F:11])([F:12])[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]([F:26])[CH:23]=[CH:22][C:21]=3[C:34]3[CH:33]=[C:32]([Br:31])[CH:37]=[CH:36][C:35]=3[O:41][CH3:42])[C@H:14]2[CH3:28])[CH:4]=[C:3]([C:2]([F:29])([F:30])[F:1])[CH:8]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 45327305-Bromo-2-methoxyphenylboronic acidHCID 59135189(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 57704830(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5'-bromo-4-fluoro-2'-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one (600 mg, 1.2 mmol), (5-bromo-2-methoxyphenyl)boronic acid (319 mg, 1.38 mmol), sodium carbonate aqueous solution (1.27 mL, 2M, 2.54 mmol), toluene (3.5 mL) and ethanol (400 μL) were mixed and stirred at room temperature for 45 minutes followed by addition of tetrakis(triphenylphosphine)palladium(0) (87 mg, 4.5 mol %). The resulting mixture was heated in a 90° C. oil bath for 24 hours to complete the reaction. The crude reaction was diluted with brine and extracted with ethyl acetate. The combined extracts were dried over Na2SO4 followed by filtration and concentration in vacuo to afford a dark oil. The crude oil was purified by reverse-phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm) eluting with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture affording (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(5′-bromo-4-fluoro-2′-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=607.04; found=607.98 (M+1)+.

Workup

  1. temperatureThe resulting mixture was heated in a 90° C. oil bath for 24 hours
  2. customthe reaction
  3. customThe crude reaction
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. filtrationfollowed by filtration and concentration in vacuo
  7. customto afford a dark oil
  8. customThe crude oil was purified by reverse-phase preparative HPLC (Kromasil 100-5C18, 100×21.1 mm)
  9. washeluting with a MeCN (0.1% TFA, v/v)/H2O (0.1% TFA, v/v) gradient mixture

Sources & evidence

ORD record
ord-f7c4083611724843a536cd1b58bbca71
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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