Ethanol → HCID 86630544, compound

HRID 607088Notes

Reaction equation

HRID 607088 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[CH2:6][N:7]1[C@H:11]([CH3:12])[C@@H:10]([C:13]2[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:16]=[CH:15][C:14]=2[C:23]2[CH:28]=[C:27](Br)[CH:26]=[CH:25][C:24]=2[O:30][CH3:31])[O:9][C:8]1=[O:32].[NH2:42][C:43]1[CH:48]=[C:47]([C:49]([O:51][CH3:52])=[O:50])[CH:46]=[CH:45][C:44]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].C(O)C>[Cl-].[Na+].O.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.Cl[Pd]Cl>[NH2:42][C:43]1[CH:48]=[C:47]([C:49]([O:51][CH3:52])=[O:50])[CH:46]=[CH:45][C:44]=1[C:27]1[CH:26]=[CH:25][C:24]([O:30][CH3:31])=[C:23]([C:14]2[CH:15]=[CH:16][C:17]([C:19]([F:21])([F:20])[F:22])=[CH:18][C:13]=2[C@H:10]2[O:9][C:8](=[O:32])[N:7]([CH2:6][C:5]3[CH:4]=[C:3]([C:2]([F:41])([F:40])[F:1])[CH:35]=[C:34]([C:36]([F:38])([F:39])[F:37])[CH:33]=3)[C@@H:11]2[CH3:12])[CH:28]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 2737801(2-Amino-4-(methoxycarbonyl)phenyl)boronic acid2×HCID 86630545HCID 86630545, compound

Product 1

HCID 86630544HCID 86630544, compound

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-5-[5′-bromo-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]-4-methyl-1,3-oxazolidin-2-one (358 mg, 0.545 mmol), [2-amino-4-(methoxycarbonyl)phenyl]boronic acid (214 mg, 1.1 mmol), dichloro bis(triphenylphosphine)palladium(II) (76.5 mg, 0.109 mmol), aqueous potassium carbonate (545 μL, 2M, 1.09 mmol) and ethanol (5 mL) were mixed and heated in a 80° C. oil bath. Aliquot at reaction time 2 hours and 3.5 hours indicated about 6% of unreacted starting material. Added more [2-amino-4-(methoxycarbonyl)phenyl]boronic acid (50 mg, 0.256 mmol) when reaction time was 3 hours 45 minutes. Aliquot did not show any further progress. Crude mixture was cooled and mixed with brine. Volatiles were removed from the crude under reduced pressure. The resulting mixture was treated with water followed by ethyl acetate extraction. The combined extracts were dried over Na2SO4, filtrated and concentrated under reduced pressure to afford a dark oil. The resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge, EtOAc/hexanes, gradient) followed by preparative TLC purification (SiO2, 10% ethyl acetate in dichloromethane) to afford methyl 2-amino-2″-{(4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-4-methyl-2-oxo-1,3-oxazolidin-5-yl}-4′-methoxy-4″-(trifluoromethyl)-1,1′:3′,1″-terphenyl-4-carboxylate. LCMS calc.=726.18; found=727.29 (M+1)+.

Workup

  1. customAliquot at reaction time 2 hours and 3.5 hours
  2. additionAdded more
  3. temperatureCrude mixture was cooled
  4. customVolatiles were removed from the crude under reduced pressure
  5. additionThe resulting mixture was treated with water
  6. extractionfollowed by ethyl acetate extraction
  7. dry with materialThe combined extracts were dried over Na2SO4
  8. filtrationfiltrated
  9. concentrationconcentrated under reduced pressure
  10. customto afford a dark oil
  11. customThe resulting oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge, EtOAc/hexanes, gradient)
  12. customfollowed by preparative TLC purification (SiO2, 10% ethyl acetate in dichloromethane)

Sources & evidence

ORD record
ord-eb28edcb6de447a5a5d5ecca273d2d12
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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