Water → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-bromo-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 607056Notes

Reaction equation

HRID 607056 reaction equation
[F:1][C:2]([F:33])([F:32])[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]=3I)[C@H:14]2[CH3:31])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:34][O:35][C:36]1[CH:41]=[CH:40][C:39]([Br:42])=[CH:38][C:37]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].O>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCCCCC.C(Cl)Cl.C1(C)C=CC=CC=1.CCO>[F:1][C:2]([F:33])([F:32])[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:41]3[CH:40]=[C:39]([Br:42])[CH:38]=[CH:37][C:36]=3[O:35][CH3:34])[C@H:14]2[CH3:31])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

10

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 45327305-Bromo-2-methoxyphenylboronic acidHCID 53363742(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 57704812(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5'-bromo-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 5

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolvent

Procedure

A mixture of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-iodo-5-(trifluoromethyl)benzyl]-4-methyl-1,3-oxazolidin-2-one (6-80 g, 11.39 mmol), 2-methoxy-5-bromo-phenyl boronic acid (3.00 g, 12.99 mmol), and sodium carbonate (2.65 g, 25.0 mmol) in 200 ml of 1:2:4 mixture of water:EtOH:toluene was stirred at room temperature for 30 min. Catalytic amount of tetrakis(triphenylphosphine) palladium (0.66 g, 5% mol) was added. The mixture was stirred under reflux for 24 h. TLC (CH2Cl2:hexane/1:1) showed no starting material. The solvents were removed. Water (100 ml) was added. The mixture was extracted with methylene chloride (3×100 ml). The combined methylene chloride layers were washed with brine and dried over sodium sulfate. The title compound was obtained after flash column using CH2Cl2:hexane/6:4 as the eluant. 1H NMR (CDCl3, 500 MHz): δ 1:1 mixture of atropisomers 7.88 (s, 1H), 7.74 (s, 1H), 7.72 (s, 1H), 7.67 (t, J=7 Hz, 1H), 7.62 (s, 1H), 7.54 (m, 1H), 7.37-7.42 (m, 1H), 7.31-7.34 (m, 1H), 6.90-6.93 (m, 1H), 5.63 (d, J=8 Hz, 0.5H), 5.25 (d, J=8 Hz, 0.5H), 4.98 (d, J=15.5 Hz, 0.5H), 4.88 (d, J=16 Hz, 0.5H), 4.12 (d, J=15.5 Hz, 0.5H), 3.88 (d, J=16.5 Hz, 0.5H), 3.84 (s, 3H), 3.81 (s, 3H), 3.73 (m, 1H), 0.59 (d, J=6.5 Hz, 1.5H), 0.45 (d, J=6.5 Hz, 1.5H).

Workup

  1. temperatureunder reflux for 24 h
  2. customThe solvents were removed
  3. additionWater (100 ml) was added
  4. extractionThe mixture was extracted with methylene chloride (3×100 ml)
  5. washThe combined methylene chloride layers were washed with brine
  6. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-71e5c9c570da4bea87b8bd78da7cd444
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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