Lithium Hydroxide → HCID 178516679, compound

HRID 1013841Notes

Reaction equation

HRID 1013841 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]([C@H: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].[C:40]1([CH:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.[Li+].[OH-]>C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:49]2[CH2:50][CH2:51][CH:46]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH2:47][CH2:48]2)[CH:5]=[C:6]([Cl:31])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([C@H:14]2[CH2:22][CH2:21][C:20]3[C:16](=[CH:17][NH:18][N:19]=3)[CH2:15]2)[C:10]1=[O:30]

Participants

5

Reactant 3

HCID 3939Lithium HydroxideHCID 698734-PhenylpiperidineHCID 87354083HCID 87354083, compound

Product 1

HCID 178516679HCID 178516679, compoundYield 48.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Heat a solution of (3R,5S)-Trifluoro-methanesulfonic acid 3,5-dichloro-4-[2-oxo-1-(2-trifluoromethanesulfonyl-4,5,6,7-tetrahydro-2H-indazol-5-yl)-pyrrolidin-3-ylmethyl]-phenyl ester (Preparation 43) (0.10 g, 0.155 mmol) and 4-phenylpiperidine (0.063 g, 0.39 mmol) in 1-methyl-2-pyrrolidine (2.5 mL) to 201° C. for 1.5 hours in a microwave reactor. Cool the reaction to room temperature and treat with 2M LiOH (1 mL) and stir for 16 hours at room temperature. Dilute the reaction with ethyl acetate and wash with water. Dry the organic layer (Na2SO4) and remove the solvent in vacuo to afford crude product. Purify with a 0 to 5% methanol in CH2Cl2 gradient to afford 0.039 g (48%) of the title compound. MS (m/z): 523 (M+).

Workup

  1. temperatureCool
  2. customthe reaction to room temperature
  3. additionDilute
  4. washwash with water
  5. dry with materialDry the organic layer (Na2SO4)
  6. customremove the solvent in vacuo
  7. customto afford crude product
  8. customPurify with a 0 to 5% methanol in CH2Cl2 gradient

Sources & evidence

ORD record
ord-dd2d241fadee4308b488cd1832e56a3e
Source dataset
uspto-grants-2011_07
Patent number
US07981918B2

Reaction notes

Loading…