Hydrochloric Acid → HCID 11607562, compound

HRID 1368278Notes

Reaction equation

HRID 1368278 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]2[C@H:12]([CH3:13])[O:11][C:10]([C:14]3[C:19]([F:20])=[CH:18][CH:17]=[CH:16][C:15]=3[F:21])=[N:9]2)=[CH:4][CH:3]=1.[F:22][C:23]([F:35])([F:34])[O:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+].Cl>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd].C(OCC)C.CCCCCC.O.C(O)C>[F:21][C:15]1[CH:16]=[CH:17][CH:18]=[C:19]([F:20])[C:14]=1[C:10]1[O:11][C@@H:12]([CH3:13])[C@@H:8]([C:5]2[CH:6]=[CH:7][C:2]([C:28]3[CH:27]=[CH:26][C:25]([O:24][C:23]([F:22])([F:34])[F:35])=[CH:30][CH:29]=3)=[CH:3][CH:4]=2)[N:9]=1

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 27343864-(Trifluoromethoxy)phenylboronic acidHCID 12056916HCID 12056916, compound

Product 1

HCID 11607562HCID 11607562, compoundYield 31%

Reagents, catalysts & solvents 5

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Conditions

Temperature
78 °C

Procedure

A 20 mL round bottom flask equipped with a magnetic stirrer, reflux condenser with nitrogen inlet and thermocouple was charged with (4R,5S)-4-(4-bromophenyl)-2-(2,6-difluorophenyl)-5-methyl-4,5-dihydro-1,3-oxazole (100 mg, 0.284 mmol), 4-(trifluoromethoxy)benzeneboronic acid (70 mg, 0.341 mmol), sodium carbonate (60 mg, 0.566 mmol), tetrakis(triphenylphosphine)palladium(O) (20 mg, 0.017 mmol) and ethyl alcohol (4 mL). The reaction mixture was heated to 78° C. for 7 hours and then cooled to 25° C. and stirred for 16 hours. 1N aq HCl (1 mL) and water (10 mL) were added, and the aqueous layer was extracted with diethyl ether (2×20 mL). The combined organic extracts were dried over sodium sulfate and concentrated under reduced pressure. Column chromatography (4:1 hexane:diethyl ether) afforded the product (38 mg, 31% yield) as a gummy solid: 1H NMR (CDCl3) δ 7.63-7.54 (m, 4H), 7.48-7.38 (m, 1H), 7.35 (d, 2H, J=8.4 Hz), 7.28 (d, 2H, J=8.4 Hz), 7.01 (t, 2H, J=8.1 Hz), 5.55 (d, 1H, J=9.9 Hz), 5.18 (m, 1H), 1.03 (d, 3H, J=6.6 Hz); EI/MS 433 m/e (M+); Chiracel OJ HPLC column shows 74% ee.

Workup

  1. customA 20 mL round bottom flask equipped with a magnetic stirrer
  2. temperaturereflux condenser with nitrogen inlet
  3. temperaturecooled to 25° C.
  4. extractionthe aqueous layer was extracted with diethyl ether (2×20 mL)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-64cde32d1e564bd899e6087eb437c11a
Source dataset
uspto-grants-2003_06
Patent number
US06573286B1

Reaction notes

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