Lithium Hydroxide → HCID 178422711, compound

HRID 1013847Notes

Reaction equation

HRID 1013847 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[C:6]([CH3:31])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:22][CH2:21][C:20]3[C:16](=[CH:17][N:18](S(C(F)(F)F)(=O)=O)[N:19]=3)[CH2:15]2)[C:10]1=[O:30].[F:40][C:41]1[CH:46]=[CH:45][C:44](B(O)O)=[CH:43][CH:42]=1.C(=O)([O-])[O-].[Na+].[Na+].[Li+].[OH-]>C1COCC1.O.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>[F:40][C:41]1[CH:46]=[CH:45][C:44]([C:4]2[CH:3]=[C:2]([CH3:1])[C:7]([CH2:8][C@@H:9]3[CH2:13][CH2:12][N:11]([CH:14]4[CH2:22][CH2:21][C:20]5[C:16](=[CH:17][NH:18][N:19]=5)[CH2:15]4)[C:10]3=[O:30])=[C:6]([CH3:31])[CH:5]=2)=[CH:43][CH:42]=1

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 86629988HCID 86629988, compound

Product 1

HCID 178422711HCID 178422711, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Purge a solution of Trifluoro-methanesulfonic acid 3,5-dimethyl-4-[(R)-2-oxo-1-(2-trifluoromethanesulfonyl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-pyrrolidin-3-ylmethyl]-phenyl ester (Preparation 66) (1.05 g, 2.2 mmol), 4-Fluorophenylboronic acid (0.38 g, 2.7 mmol), and sodium carbonate (0.36 g, 3.4 mmol) in THF (15 mL) and water (5 mL) with nitrogen. Treat the reaction with Tetrakis(triphenylphosphine)palladium(0) (0.13 g, 0.1 mmol) and again purge with nitrogen. Heat the reaction to 80° C. and stir for 2 hr. Treat the reaction with 1N LiOH (5 mL) and cool to room temperature. Quench the reaction with 1N HCl. Extract the aqueous with EtOAc. Wash the organic with brine, dry over MgSO4, and filter. Purify the crude by silica gel column chromatography using CH2Cl2 and 2M Ammonia in MeOH to elute the pure product. MS (m/e): 418 (M+1).

Workup

  1. additionTreat
  2. customagain purge with nitrogen
  3. temperatureHeat
  4. customthe reaction to 80° C.
  5. additionTreat
  6. customQuench
  7. customthe reaction with 1N HCl
  8. extractionExtract the aqueous with EtOAc
  9. washWash the organic with brine
  10. dry with materialdry over MgSO4
  11. filtrationfilter
  12. customPurify the crude by silica gel column chromatography
  13. washto elute the pure product

Sources & evidence

ORD record
ord-0f1fe3a1a763488a82e396040e712128
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

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