Acetic Acid → HCID 75096360, compound

HRID 1807110Notes

Reaction equation

HRID 1807110 reaction equation
C([Si](C)(C)[O:6][CH2:7][CH2:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([CH:17]2[CH:21]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=3)[C:20]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=3)([C:29]#[N:30])[CH:19]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[NH:18]2)=[O:16])=[N:10]1)(C)(C)C.C(O)(=O)C.O>CCOC(C)=O>[OH:6][CH2:7][CH2:8][N:9]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([CH:17]2[CH:21]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[CH:23]=3)[C:20]([C:31]3[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=3)([C:29]#[N:30])[CH:19]([CH2:38][C:39]([CH3:42])([CH3:41])[CH3:40])[NH:18]2)=[O:16])=[N:10]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 962WaterHCID 72272555HCID 72272555, compound

Product 1

HCID 75096360HCID 75096360, compoundYield 40.22%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid {1-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-1H-pyrazol-3-yl}-amide (65.2 mg, 0.0995 mmol), acetic acid (2.0 mL, 31 mmol), water (1 mL) and stirred at RT over the weekend (48 h). Reaction complete by 50%. The mixture was then diluted with EtOAc and washed with NaHCO3(s). The organic phase was separated, filtered and dried over Na2SO4. The mixture was then concentrated under reduced vacuum and purified by reverse phase chromatography (20-95% of ACN/water) to give rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [1-(2-hydroxy-ethyl)-1H-pyrazol-3-yl]-amide (21.6 mg, 40.22%) as a white powder.

Workup

  1. customReaction complete by 50%
  2. washwashed with NaHCO3(s)
  3. customThe organic phase was separated
  4. filtrationfiltered
  5. dry with materialdried over Na2SO4
  6. concentrationThe mixture was then concentrated under reduced vacuum
  7. custompurified by reverse phase chromatography (20-95% of ACN/water)

Sources & evidence

ORD record
ord-742a63b64a4f4a2da6678d3f94dbe0b7
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

Loading…