Sodium Carbonate → HCID 57671358, compound

HRID 1013852Notes

Reaction equation

HRID 1013852 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[C:6]([Cl:31])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:22][CH2:21][CH2:20][C:19]3[N:18](S(C(F)(F)F)(=O)=O)[N:17]=[CH:16][C:15]2=3)[C:10]1=[O:30].ClC1C=C(OS(C(F)(F)F)(=O)=O)C=C(Cl)C=1C[C@@H]1CCN(C2CCCC3C2=CN(S(C(F)(F)F)(=O)=O)N=3)C1=O.[F:79][C:80]([F:91])([F:90])[C:81]1[CH:86]=[CH:85][C:84](B(O)O)=[CH:83][CH:82]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.O.C(OCC)(=O)C.[Li+].[OH-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:84]2[CH:85]=[CH:86][C:81]([C:80]([F:91])([F:90])[F:79])=[CH:82][CH:83]=2)[CH:5]=[C:6]([Cl:31])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:22][CH2:21][CH2:20][C:19]3[NH:18][N:17]=[CH:16][C:15]2=3)[C:10]1=[O:30]

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 86629990HCID 86629990, compoundHCID 86629991HCID 86629991, compound

Product 1

HCID 57671358HCID 57671358, compound

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3939Lithium HydroxideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

Bring a mixture of trifluoro-methanesulfonic acid 3,5-dichloro-4-[(R)-2-oxo-1-(1-trifluoromethanesulfonyl-4,5,6,7-tetrahydro-1H-indazol-4-yl)-pyrrolidin-3-ylmethyl]phenyl ester and trifluoro-methanesulfonic acid 3,5-dichloro-4-[(R)-2-oxo-1-(2-trifluoromethanesulfonyl-4,5,6,7-tetrahydro-2H-indazol-4-yl)-pyrrolidin-3-ylmethyl]-phenyl ester (0.5 g, 0.78 mmol), 4-trifluoromethylphenylboronic acid (0.18 g, 0.93 mmol), sodium carbonate (0.25 g, 2.3 mmol) in THF (15 mL) and water (5 mL) to 60° C. To the mixture at 60° C., add Pd(PPh3)4 (0.04 g, 0.03 mmol). Raise the reaction temperature to 80° C. and stir the reaction for 1 hour. Cool the reaction, dilute with ethyl acetate, and wash with water and brine. Dry the organic layer (Na2SO4) and remove the solvent in vacuo to afford crude product (0.48 g). Dissolve in THF (5 mL) and stir in LiOH (2 N, 3 mL) at room temperature for 1.5 hour. Quench the reaction with HCl (1N, 8 mL), dilute with ethyl acetate, and wash with water. Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and then purify on silica gel column with 100% dichloromethane to 10% methanol in dichloromethane to afford 0.35 g of the title product. MS (m/z): 508 (M+).

Workup

  1. customthe reaction for 1 hour
  2. temperatureCool
  3. customthe reaction
  4. washwash with water and brine
  5. dry with materialDry the organic layer (Na2SO4)
  6. customremove the solvent in vacuo
  7. customto afford crude product (0.48 g)
  8. customQuench
  9. customthe reaction with HCl (1N, 8 mL)
  10. washwash with water
  11. dry with materialDry the organic layer (Na2SO4)
  12. customremove the solvent in vacuo
  13. customto afford crude product
  14. custompurify on silica gel column with 100% dichloromethane to 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-feb80350c70142d5a37dfc7fd0d8f2ae
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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