Acetic Acid → HCID 75096416, compound

HRID 1807117Notes

Reaction equation

HRID 1807117 reaction equation
[CH3:1][S:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]([CH:9]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)[C:12]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)([C:21]#[N:22])[CH:11]([CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[NH:10]1)=[O:8].C(O)(=[O:37])C.OO.[OH2:41]>ClCCl.[Zn]>[CH3:1][S:2]([CH2:3][CH2:4][CH2:5][NH:6][C:7]([CH:9]1[CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)[C:12]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)([C:21]#[N:22])[CH:11]([CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[NH:10]1)=[O:8])(=[O:37])=[O:41]

Participants

7

Reactant 4

HCID 176Acetic Acid2×HCID 784Hydrogen PeroxideHCID 962WaterHCID 77261880HCID 77261880, compound

Product 1

HCID 75096416HCID 75096416, compoundYield 28.8%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 6344DichloromethaneSolvent2×

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 (3-methylsulfanyl-propyl)-amide (119.2 mg, 0.23 mmol) and dichloromethane (2 mL) was added to a solution of refluxing acetic acid (5 mL, 79.4 mmol) and 30% hydrogen peroxide (2 mL) for 5 min. The reaction mixture was cooled to room temperature and stored in the freezer overnight. The mixture was diluted with water and dichloromethane, the organic layer was separated and solvent removed under reduced pressure. The resulting oil was carried directly to the next step by adding acetic acid (5 mL, 79.4 mmol) and zinc dust (0.85 g, 13 mmol). After stirring at room temperature for 3 h, an additional amount of zinc dust (0.85 g, 13 mmol) was added and stirred for an additional 3 h at room temperature. Reaction worked up by filtration through celite, washing with dichloromethane (50 mL). The filtrate was washed with water (2×) and the organic layer was separated, dried with MgSO4, filtered and the solvent evaporated under reduced pressure to yield crude oil. Purification 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 (3-methanesulfonyl-propyl)-amide (36.5 mg, 28.8%) as an off-white powder. HRMS (ES+) m/z Calcd for C27H33Cl2N3O3S+H [(M+H)+]: 550.1693. found: 550.1692.

Workup

  1. customstored in the freezer overnight
  2. customthe organic layer was separated
  3. customsolvent removed under reduced pressure
  4. stirringstirred for an additional 3 h at room temperature
  5. customReaction
  6. filtrationworked up by filtration through celite
  7. washwashing with dichloromethane (50 mL)
  8. washThe filtrate was washed with water (2×)
  9. customthe organic layer was separated
  10. dry with materialdried with MgSO4
  11. filtrationfiltered
  12. customthe solvent evaporated under reduced pressure
  13. customto yield crude oil
  14. customPurification by reverse phase chromatography (20-95% of ACN/water)

Sources & evidence

ORD record
ord-c81d9aed2b194c4c89622be8b8d39237
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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