tert-Butyl methyl ether → HCID 86670385, compound

HRID 1972529Notes

Reaction equation

HRID 1972529 reaction equation
[C:1]1([S:7]([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[Na+].Br[C:23]1[CH:28]=[CH:27][C:26]([C:29]([OH:38])([C:34]([F:37])([F:36])[F:35])[C:30]([F:33])([F:32])[F:31])=[CH:25][CH:24]=1.COC(C)(C)C>C1(C)C=CC=CC=1>[F:31][C:30]([F:32])([F:33])[C:29]([C:26]1[CH:25]=[CH:24][C:23]([N:13]2[CH2:12][CH2:11][CH:10]([S:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)(=[O:9])=[O:8])[CH2:15][CH2:14]2)=[CH:28][CH:27]=1)([OH:38])[C:34]([F:35])([F:37])[F:36]

Participants

6

Reactant 4

HCID 15413tert-Butyl methyl etherHCID 5190868HCID 5190868, compoundHCID 232335702-(4-Bromophenyl)-1,1,1,3,3,3-hexafluoropropan-2-olHCID 23676156Sodium t-butoxide

Product 1

HCID 86670385HCID 86670385, compoundYield 89.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

A 15-mL reaction vial was charged with 4-(phenylsulfonyl)piperidine (1.05 g, 4.66 mmol, BetaPharma, Brandford, Conn.), sodium t-butoxide (0.98 g, 10.24 mmol), 2-(4-bromophenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (1.50 g, 4.66 mmol, Bioorg. Med. Chem. Lett. 2002, 12, 3009), chloro(2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II), methyl-t-butylether adduct (RuPhos Palladacycle) (0.170 g, 0.233 mmol, Strem Chemicals, Inc, Newburyport, Mass.), and toluene (10 mL). The vial was closed and purged with nitrogen for several minutes. The reaction mixture was heated at 100° C. for 2.5 h and allowed to cool to room temperature. The reaction mixture was diluted with water (5 mL) and extracted with EtOAc (10 mL). The organic extract was washed with water (5 mL) and dried over Na2SO4. The solution was filtered and concentrated and then absorbed onto a plug of silica gel and purified by column chromatography (40 g of silica gel, 10 to 30% EtOAc in hexanes) to provide 1,1,1,3,3,3-hexafluoro-2-(4-(4-(phenylsulfonyl)piperidin-1-yl)phenyl)-2-propanol (1.94 g) as white solid

Workup

  1. customA 15-mL reaction
  2. customThe vial was closed
  3. custompurged with nitrogen for several minutes
  4. temperatureto cool to room temperature
  5. additionThe reaction mixture was diluted with water (5 mL)
  6. extractionextracted with EtOAc (10 mL)
  7. extractionThe organic extract
  8. washwas washed with water (5 mL)
  9. dry with materialdried over Na2SO4
  10. filtrationThe solution was filtered
  11. concentrationconcentrated
  12. customabsorbed onto a plug of silica gel
  13. custompurified by column chromatography (40 g of silica gel, 10 to 30% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f30c314bfadb4c6d80ea8fae71208128
Source dataset
uspto-grants-2013_04
Patent number
US08431563B2

Reaction notes

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