Hydrochloric Acid → 5-[4-Chloro-2-(trifluoromethyl)phenyl]-1-[(1R,2S)-2-hydroxy-1-methylpropyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide

HRID 451365Notes

Reaction equation

HRID 451365 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:12][CH:11]=[C:10]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][CH:17]=3)=[O:14])[C:9]=2[CH3:26])=[C:4]([C:27]([F:30])([F:29])[F:28])[CH:3]=1.CC(C)([O-])C.[Na+].[CH3:37][C@H:38]1[C@H:42]([CH3:43])OS(=O)(=O)[O:39]1.Cl>CC(N(C)C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C@H:42]([CH3:43])[C@@H:38]([OH:39])[CH3:37])[CH:11]=[C:10]([C:13]([NH:15][C:16]3[CH:17]=[CH:18][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:20][CH:21]=3)=[O:14])[C:9]=2[CH3:26])=[C:4]([C:27]([F:29])([F:28])[F:30])[CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 13545565(4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxideHCID 23676156Sodium t-butoxideHCID 584885155-[4-chloro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide

Product 1

HCID 451389565-[4-Chloro-2-(trifluoromethyl)phenyl]-1-[(1R,2S)-2-hydroxy-1-methylpropyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamideYield 44%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent2×

Procedure

To a solution of 5-[4-chloro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide (21 g, 47 mmol) in anhydrous DMA (234 ml) was added sodium tert-butoxide (10 g, 0.11 mol) and stirred at room temperature for 30 min under N2. (4S,5S)-4,5-dimethyl-1,3,2-dioxathiolane 2,2-dioxide (11 g, 70 mmol) in anhydrous DMA (50 ml) was added to the solution and stirred at 70° C. for 2.0 h. The reaction mixture was cooled to 0° C. and added 2N HCl (100 ml) and concentrated on a rotary evaporator. To this residue was added anhydrous THF (120 ml) and 5N HCl (120 ml) and stirred at 60° C. for 90 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 (1:1 to 1:9 hexane:ethyl acetate) to give an atropisomeric mixture of the title compound (10.9 g, 44%) as a white solid.

Workup

  1. stirringstirred at 70° C. for 2.0 h
  2. temperatureThe reaction mixture was cooled to 0° C.
  3. concentrationconcentrated on a rotary evaporator
  4. additionTo this residue was added anhydrous THF (120 ml) and 5N HCl (120 ml)
  5. stirringstirred at 60° C. for 90 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 (1:1 to 1:9 hexane:ethyl acetate)
  11. customto give

Sources & evidence

ORD record
ord-bedd60ac3ffc435785b4936ad68026f4
Source dataset
uspto-grants-2013_07
Patent number
US08487117B2

Reaction notes

Loading…