Dichloromethane → Methyl 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6'-fluoro-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

HRID 607098Notes

Reaction equation

HRID 607098 reaction equation
[F:1][C:2]([F:41])([F:40])[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]=3B3OC(C)(C)C(C)(C)O3)[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C.[F:43][C:44]1[CH:49]=[C:48]([O:50][CH3:51])[C:47](I)=[CH:46][C:45]=1[C:53]1[CH:58]=[CH:57][C:56]([C:59]([O:61][CH3:62])=[O:60])=[CH:55][C:54]=1[CH3:63].C(=O)([O-])[O-].[Na+].[Na+].C(Cl)Cl>O.CCO.C1(C)C=CC=CC=1.[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>[F:41][C:2]([F:1])([F:40])[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:27])([F:28])[F:29])[CH:23]=[CH:22][C:21]=3[C:47]3[CH:46]=[C:45]([C:53]4[CH:58]=[CH:57][C:56]([C:59]([O:61][CH3:62])=[O:60])=[CH:55][C:54]=4[CH3:63])[C:44]([F:43])=[CH:49][C:48]=3[O:50][CH3:51])[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:10])([F:12])[F:11])[CH:8]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 57704825Methyl 2'-fluoro-5'-iodo-4'-methoxy-2-methylbiphenyl-4-carboxylateHCID 86630539HCID 86630539, compound2×

Product 1

HCID 57704858Methyl 2''-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-6'-fluoro-4'-methoxy-2-methyl-4''-(trifluoromethyl)-1,1':3',1''-terphenyl-4-carboxylate

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8058HexaneSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

(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-methane (1.30 g, 2.18 mmol) (INTERMEDIATE 9), the title compound from Step B (1.30 g, 3.25 mmol), tetrakis(triphenylphosphine) palladium (250 mg, 10% mol) and sodium carbonate (507 mg, 4.79 mmol) in 50 ml of water/EtOH/toluene (1:2:4) was heated to reflux for 4 h. TLC (CH2Cl2:hexane/1:1) showed that the reaction was complete. The solvents were removed. Water (20 ml) was added. The organic was extracted with methylene chloride (3×30 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/8:2 as the elute. 1H NMR (CDCl3, 500 MHz): δ a mixture of 1:1 atopoisomers 7.98 (d, J=4.5 Hz, 1H), 7.89 (s, 2H), 7.68 (m, 4H), 7.42 (t, J=6.0 Hz, 1H), 7.30 (d, J=7.5 Hz, 0.5H), 7.26 (d, J=7.5 Hz, 0.5H), 7.07 (t, J=8.0 Hz, 1H), 6.87 (d, J=5.5 Hz, 0.5H), 6.85 (d, J=6.0 Hz, 0.5H), 5.63 (d, J=8.0 Hz, 0.5H), 5.41 (d, J=8.0 Hz, 0.5H), 5.00 (d, J=15.5 Hz, 0.5H), 4.92 (d, J=16.0 Hz, 0.5H), 4.17 (d, J=15.5 Hz, 0.5H), 3.95 (d, J=16.0 Hz, 0.5H), 3.95 (s, 3H), 3.88 (s, 3H), 3.84 (m, 1H), 2.32 (s, 1.5H), 2.28 (s, 1.5H), 0.64 (d, J=7.0 Hz, 1.5H), 0.62 (d, J=6.5 Hz, 1.5H). LC/MS M+744.2

Workup

  1. temperatureto reflux for 4 h
  2. customThe solvents were removed
  3. additionWater (20 ml) was added
  4. extractionThe organic was extracted with methylene chloride (3×30 ml)
  5. washThe combined methylene chloride layers were washed with brine
  6. dry with materialdried over sodium sulfate

Sources & evidence

ORD record
ord-fd6e6b6bbe7c49b0939003a132a102e9
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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