1,2-Dichloroethane → HCID 42602916, compound

HRID 888368Notes

Reaction equation

HRID 888368 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH:14]([OH:19])[C:15]([F:18])([F:17])[F:16])[CH:11]=[C:10]([C:20]([OH:22])=O)[CH:9]=2)=[CH:4][CH:3]=1.C1C=NC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[F:42][C:43]([F:47])([F:46])[CH2:44][NH2:45].C(Cl)CCl.C([O-])(O)=O.[Na+].[Li+].[Cl-]>CCOC(C)=O.CN(C=O)C>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH:14]([OH:19])[C:15]([F:16])([F:18])[F:17])[CH:11]=[C:10]([C:20]([NH:45][CH2:44][C:43]([F:47])([F:46])[F:42])=[O:22])[CH:9]=2)=[CH:4][CH:3]=1

Participants

10

Reactant 7

HCID 111,2-DichloroethaneHCID 9773Ethanamine, 2,2,2-trifluoro-HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 433294Lithium ChlorideHCID 516892Sodium BicarbonateHCID 68500068HCID 68500068, compound

Product 1

HCID 42602916HCID 42602916, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a DMF solution (9.7 mL) containing 4′-methyl-5-(2,2,2-trifluoro-1-hydroxyethyl)biphenyl-3-carboxylic acid (300 mg, 0.97 mmol), HOAt (1.6 mL, 0.97 mmol), DIPEA (0.34 mL, 1.9 mmol), and 2,2,2-trifluoroethanamine (0.23 mL, 2.9 mmol) was added EDC (278 mg, 1.45 mmol). The reaction was stirred at room temperature overnight. EtOAc, NaHCO3 and 3M LiCl were added to the reaction and organics were extracted with EtOAc (3×). The combined organic layers were washed with 3M LiCl (3×) and followed by brine. The final organic layer was dried over Na2SO4, filtered and concentrated. Crude product was taken up in DMF and purified by RP-HPLC. Fractions containing product were combined and sat. NaHCO3 and EtOAc were added. Organics were extracted with EtOAc and washed with brine. Final organic layer was dried over Na2SO4, filtered and concentrated to give a white solid: 1H NMR (CD3OD, 400 MHz) δ 8.07 (s, 1H), 7.93 (s, 1H), 7.90 (s, 1H), 7.55 (d, J=8.2 Hz, 2H), 7.27 (d, J=7.9 Hz, 2H), 5.16 (q, J=7.1 Hz, 1H), 4.09 (q, J=9.2 Hz, 2H), 2.36 (s, 3H); HRMS (ES, M+H) calcd for C18H15F6NO2: 392.1080. found: 392.1079.

Workup

  1. extractionorganics were extracted with EtOAc (3×)
  2. washThe combined organic layers were washed with 3M LiCl (3×)
  3. dry with materialThe final organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by RP-HPLC
  7. additionFractions containing product
  8. additionsat. NaHCO3 and EtOAc were added
  9. extractionOrganics were extracted with EtOAc
  10. washwashed with brine
  11. dry with materialFinal organic layer was dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto give a white solid

Sources & evidence

ORD record
ord-c6e587836741448b9c271214e3633314
Source dataset
uspto-grants-2012_08
Patent number
US08247401B2

Reaction notes

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