Lithium Hydroxide → HCID 57671406, compound

HRID 1013849Notes

Reaction equation

HRID 1013849 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[C:22]3[N:21](S(C(F)(F)F)(=O)=O)[N:20]=[CH:19][C:18]=3[CH2:17][CH2:16][CH2:15]2)[C:10]1=[O:30].ClC1C=C(OS(C(F)(F)F)(=O)=O)C=C(Cl)C=1C[C@@H]1CCN(C2C3C(=CN(S(C(F)(F)F)(=O)=O)N=3)CCC2)C1=O.[F:79][C:80]1[CH:85]=[CH:84][C:83](B(O)O)=[CH:82][CH:81]=1.C(=O)([O-])[O-].[Na+].[Na+].[Li+].[OH-]>C1COCC1.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.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:83]2[CH:84]=[CH:85][C:80]([F:79])=[CH:81][CH:82]=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[C:22]3[NH:21][N:20]=[CH:19][C:18]=3[CH2:17][CH2:16][CH2:15]2)[C:10]1=[O:30]

Participants

9

Reactant 5

HCID 3939Lithium HydroxideHCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 57671331HCID 57671331, compoundHCID 57671374HCID 57671374, compound

Product 1

HCID 57671406HCID 57671406, compoundYield 63%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Purge a solution of trifluoro-methanesulfonic acid 3,5-dichloro-4-[(R)-2-oxo-1-(1-trifluoromethanesulfonyl-4,5,6,7-tetrahydro-1H-indazol-7-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-7-yl)-pyrrolidin-3-ylmethyl]-phenyl ester (Preparation 79) (1.64 g, 2.54 mmol), 4-fluorophenylboronic acid (0.427 g, 3.05 mmol), and 2M sodium carbonate (3.8 mL) in THF (63 mL) with nitrogen. Treat the reaction with tetrakis(triphenylphosphine)palladium(0) (0.147 g, 0.127 mmol) and heat the reaction to 80° C. and stir for 1 hr. Cool to room temperature and treat the reaction with 2N LiOH (12.7 mL) and stir for 1 hr. Dilute the reaction with water and extract with ethyl acetate. The organic layer is dried (Na2SO4) and the solvent is removed to afford crude product that is purified first with 0 to 10% methanol in CH2Cl2 and then with a Varian 10 g SCX column with 9/1 CH2Cl2/MeOH and then 2:1 CH2Cl2/2M NH3 in MeOH to afford 0.735 g (63%) of the titled product. MS (m/z): 458 (M+1).

Workup

  1. additionTreat
  2. temperatureheat
  3. customthe reaction to 80° C.
  4. additiontreat
  5. stirringstir for 1 hr
  6. additionDilute
  7. extractionextract with ethyl acetate
  8. dry with materialThe organic layer is dried (Na2SO4)
  9. customthe solvent is removed
  10. customto afford crude product that
  11. customis purified first with 0 to 10% methanol in CH2Cl2

Sources & evidence

ORD record
ord-abe1cdb104634633af5e550b1b97d5e7
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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