Acetone → HCID 86640466, compound

HRID 1807104Notes

Reaction equation

HRID 1807104 reaction equation
[CH3:1][C:2]([O:41][CH2:42][C@@H:43]1[CH2:45][O:44]1)([CH3:40])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[F:24])[C:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[CH:14]([CH2:35][C:36]([CH3:39])([CH3:38])[CH3:37])[NH:13]2)=[O:11])=[N:5]1.O.CC(C)=[O:49].Cl(O)(=O)(=O)=O>C(OCC)(=O)C>[OH:49][C@@H:43]([CH2:45][OH:44])[CH2:42][O:41][C:2]([CH3:40])([CH3:1])[CH2:3][N:4]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([CH:12]2[CH:16]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([Cl:23])[C:18]=3[F:24])[C:15]([C:27]3[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:28]=3[F:34])([C:25]#[N:26])[CH:14]([CH2:35][C:36]([CH3:39])([CH3:37])[CH3:38])[NH:13]2)=[O:11])=[N:5]1

Participants

6

Reactant 4

HCID 180AcetoneHCID 962WaterHCID 24247Perchloric Acid2×HCID 86640463HCID 86640463, compound

Product 1

HCID 86640466HCID 86640466, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethylpropyl)-pyrrolidine-2-carboxylic acid {1-[2-methyl-2-((S)-1-oxiranylmethoxy)-propyl]-1H-pyrazol-3-yl}-amide (51.2 mg, 0.078 mmol), water (2 mL), and acetone (10 mL) was cooled to 0° C., then a solution of 35% perchloric acid (0.1 mL) was added dropwise. The reaction was stirred an additional 0.5 h. Then an additional 1 mL of the 35% perchloric acid solution was added at 0° C., the reaction was allowed to warm to rt for 12 h. The mixture was then diluted with ethyl acetate and washed with sodium bicarbonate (sat'd). The organic phase was separated, dried over Na2SO4 and filtered. The mixture was then concentrated and purified by reverse phase chromatography (20-95% of ACN/water) to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid {1-[2-((S)-2,3-dihydroxy-propoxy)-2-methyl-propyl]-1H-pyrazol-3-yl}-amide (22.1 mg, 42%) as an white powder. HRMS (ES+) m/z Calcd for C33H39Cl2F2N5O4S+H [(M+H)+]: 678.2420. found: 078.2416; C33H39Cl2F2N5O4+[(Na+H)+]: 700.2239. found: 700.2235.

Workup

  1. temperatureto warm to rt for 12 h
  2. washwashed with sodium bicarbonate (sat'd)
  3. customThe organic phase was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe mixture was then concentrated
  7. custompurified by reverse phase chromatography (20-95% of ACN/water)

Sources & evidence

ORD record
ord-8bb2245afb9f42e0923727fd53102abb
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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