Sodium Bicarbonate → 2-(4-((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

HRID 1972593Notes

Reaction equation

HRID 1972593 reaction equation
[N+:1]([C:4]1[S:8][C:7]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([OH:33])([C:29]([F:32])([F:31])[F:30])[C:25]([F:28])([F:27])[F:26])=[CH:20][CH:19]=3)[C@@H:14]([CH2:34][N:35]3[CH2:40][CH2:39][O:38][CH2:37][C@@H:36]3[CH3:41])[CH2:13]2)(=[O:11])=[O:10])=[CH:6][CH:5]=1)([O-])=O.C([O-])(O)=O.[Na+]>[Fe].C(O)(=O)C>[NH2:1][C:4]1[S:8][C:7]([S:9]([N:12]2[CH2:17][CH2:16][N:15]([C:18]3[CH:19]=[CH:20][C:21]([C:24]([OH:33])([C:29]([F:32])([F:30])[F:31])[C:25]([F:27])([F:28])[F:26])=[CH:22][CH:23]=3)[C@@H:14]([CH2:34][N:35]3[CH2:40][CH2:39][O:38][CH2:37][C@@H:36]3[CH3:41])[CH2:13]2)(=[O:10])=[O:11])=[CH:6][CH:5]=1

Participants

5

Reactant 2

HCID 516892Sodium BicarbonateHCID 866704002-(4-((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol

Product 1

HCID 569328792-(4-((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanolYield 68.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
50 °C

Procedure

A 5-mL vial was charged with 2-(4-((2S)-4-((5-nitro-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.060 g, 0.094 mmol, step 5), iron filings (0.0282 g, 0.505 mmol, Sigma-Aldrich, St. Louis, Mo.) and acetic acid (2 mL). The mixture was stirred at 50° C. for 40 min. Saturated aqueous NaHCO3 (20 mL) was added slowly and then the aqueous phase was extracted with EtOAc (2×20 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (twice, 25 g of silica gel, 30 to 90% EtOAc in hexanes then 10 g of silica gel, 30 to 90% EtOAc in hexanes) to afford 2-(4-((2S)-4-((5-amino-2-thiophenyl)sulfonyl)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-1-piperazinyl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (0.0386 g) as a white solid.

Workup

  1. extractionthe aqueous phase was extracted with EtOAc (2×20 mL)
  2. dry with materialThe combined organic extracts were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography (twice, 25 g of silica gel, 30 to 90% EtOAc in hexanes

Sources & evidence

ORD record
ord-4b3853ea00aa4cfd8738376d80c77190
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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