Hydrochloric Acid → HCID 45380876, compound

HRID 451369Notes

Reaction equation

HRID 451369 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][CH:12]=[C:11]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[O:15])[C:10]=1[CH3:27].CC(C)([O-])C.[Na+].[CH3:34][C@H:35]1[C@H:39]([CH3:40])OS(=O)(=O)[O:36]1.Cl>CC(N(C)C)=O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:13]([C@H:39]([CH3:40])[C@@H:35]([OH:36])[CH3:34])[CH:12]=[C:11]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)=[O:15])[C:10]=1[CH3:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 13545565(4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxideHCID 23676156Sodium t-butoxideHCID 58488524HCID 58488524, compound

Product 1

HCID 45380876HCID 45380876, compoundYield 50.5%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

To a solution of 5-(2-chloro-4-fluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide (0.50 g, 1.2 mmol) in anhydrous DMA (8.0 ml) was added sodium tert-butoxide (0.27 g, 2.8 mmol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (0.28 g, 1.8 mmol) in anhydrous DMA (2.0 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to room temperature and added 2N HCl (2.0 ml) and concentrated on a rotary evaporator. To this residue was added anhydrous THF (4.0 ml) and 5N HCl (5.0 ml) and stirred at 60° C. for 80 min. The mixture was diluted with ethyl acetate and washed with water, satd NaHCO3 and brine, then dried over sodium sulfate and concentrated on a rotary evaporator. The resulting residue was purified by silica-gel column chromatography (3:7 to 2:8 hexane:ethyl acetate) to give an atropisomeric mixture of the title compound (0.29 g, 50%) as a white solid.

Workup

  1. stirringstirred at 70° C. for 2.0 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated on a rotary evaporator
  4. additionTo this residue was added anhydrous THF (4.0 ml) and 5N HCl (5.0 ml)
  5. stirringstirred at 60° C. for 80 min
  6. additionThe mixture was diluted with ethyl acetate
  7. washwashed with water
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated on a rotary evaporator
  10. customThe resulting residue was purified by silica-gel column chromatography (3:7 to 2:8 hexane:ethyl acetate)
  11. customto give

Sources & evidence

ORD record
ord-e04dfc653a074b49a7da9cd99ff8e9b7
Source dataset
uspto-grants-2013_07
Patent number
US08487117B2

Reaction notes

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