1,1,1,3,3,3-Hexafluoro-2-propanol → HCID 57656444, compound

HRID 2041104Notes

Reaction equation

HRID 2041104 reaction equation
[F:1][N+]1C(C(F)(F)F)=CC(C(F)(F)F)=CC=1S([O-])(=O)=O.[OH:20][C:21]1[C:31]2[CH2:30][CH2:29][N:28]([C:32](=[O:37])[C:33]([F:36])([F:35])[F:34])[CH2:27][CH2:26][C:25]=2[CH:24]=[CH:23][CH:22]=1.C(O)(C(F)(F)F)C(F)(F)F>C(Cl)Cl>[F:1][C:22]1[CH:23]=[CH:24][C:25]2[CH2:26][CH2:27][N:28]([C:32](=[O:37])[C:33]([F:36])([F:34])[F:35])[CH2:29][CH2:30][C:31]=2[C:21]=1[OH:20]

Participants

5

Reactant 3

HCID 135291,1,1,3,3,3-Hexafluoro-2-propanolHCID 27372911-Fluoro-4,6-bis(trifluoromethyl)pyridin-1-ium-2-sulfonateHCID 22219609HCID 22219609, compound

Product 1

HCID 57656444HCID 57656444, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add N-fluoro-4,6-bis(trifluoromethyl)-pyridinium 2-sulfonate (3.02 g, 9.6 mmol) to a stirred mixture of 6-hydroxy-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (2.5 g, 9.6 mmol) and hexafluoro-2-propanol (10 mL) in DCM (150 mL). Stir at ambient temperature for 16 h. Concentrate the reaction mixture and partition the residue between EtOAc and 1N aqueous HCl. Wash the organic fraction with saturated aqueous NaHCO3, brine, dry over Na2SO4, filter and concentrate. Purify by chromatography on silica gel eluting with hexane/EtOAc (20:1, 10:1, 6:1, 5:1 and 3:1) to give 7-fluoro-6-hydroxy-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a white solid (1.8 g, 68%). Dissolve 7-fluoro-6-hydroxy-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (1.5 g, 5.41 mmol) in a mixture of DCM (20 mL) and pyridine (2 mL) and cool in an ice bath. Add dropwise to the stirred solution a mixture of trifluoromethanesulfonic anhydride (1.64 mL, 9.74 mmol) in DCM and stir the reaction for 1.5 h at ambient temperature. Dilute the reaction with DCM (300 mL) and wash with 2.5N aqueous HCl. Dry the organic fraction over Na2SO4, filter and concentrate to give the title product as a white solid (2.2 g, 99%). MS (ES+) m/z: 410 (M+H)+.

Workup

  1. concentrationConcentrate the reaction mixture
  2. custompartition the residue between EtOAc and 1N aqueous HCl
  3. washWash the organic fraction with saturated aqueous NaHCO3, brine
  4. dry with materialdry over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by chromatography on silica gel eluting with hexane/EtOAc (20:1, 10:1, 6:1, 5:1 and 3:1)

Sources & evidence

ORD record
ord-9a3481cbc21c4082abdb5652546f92cb
Source dataset
uspto-grants-2013_11
Patent number
US08580780B2

Reaction notes

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