Hydrochloric Acid → HCID 86732259, compound

HRID 930420Notes

Reaction equation

HRID 930420 reaction equation
CC([S@]([NH:7][C@:8]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[C:19]=1[F:25])([CH2:11][C@H:12]([OH:17])[C:13]([F:16])([F:15])[F:14])[CH2:9][F:10])=O)(C)C.Cl.O1CCOCC1>C(Cl)Cl.CO>[NH2:7][C@@:8]([C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH3:24])[C:19]=1[F:25])([CH2:9][F:10])[CH2:11][C@H:12]([OH:17])[C:13]([F:15])([F:16])[F:14]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 86732258HCID 86732258, compound

Product 1

HCID 86732259HCID 86732259, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-2-methyl-N-((2S,4S)-1,5,5,5-tetrafluoro-2-(2-fluoro-3-methylphenyl)-4-hydroxypentan-2-yl)propane-2-sulfinamide (2.0 g, 5.16 mmol) in DCM (20 mL) and MeOH (10 mL) was added hydrogen chloride, 4.0m solution in 1,4-dioxane (12.91 ml, 51.6 mmol) and stirred at rt for 15 min. The reaction went to completion, concentrated, diluted with DCM and washed with 1N NaOH. The organic phase was separated, dried over Na2SO4, filtered and concentrated to afford (2S,4S)-4-amino-1,1,1,5-tetrafluoro-4-(2-fluoro-3-methylphenyl)pentan-2-ol. This amino-alcohol was dissolved in THF (12 mL) followed by the addition of benzoyl isothiocyanate (0.764 ml, 5.68 mmol) and the resulting mixture was stirred at rt for 40 min. The reaction went to completion then triethylamine (0.862 ml, 6.20 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hcl (1.089 g, 5.68 mmol) were added and the resulting mixture was heated at 70° C. for 1 h. The reaction went to completion. The mixture was diluted with water and extracted with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-20% EtOAc/hexanes to afford a white solid as N-((4S,6S)-4-(2-fluoro-3-methylphenyl)-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide (1.69 g, 4.10 mmol, 79% yield). MS m/z=412.9 [M+H]+. Calculated for C20H17F5N2O2S: 412.12.

Workup

  1. concentrationconcentrated
  2. additiondiluted with DCM
  3. washwashed with 1N NaOH
  4. customThe organic phase was separated
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-e4c18d4390d0430e89db52f86a62d990
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

Loading…