Hydrochloric Acid → HCID 86728107, compound

HRID 627638Notes

Reaction equation

HRID 627638 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:27])=[C:6]([C:8]([NH:20]S(C(C)(C)C)=O)([CH2:18][F:19])[CH2:9][S:10]([C:13]([C:16]#[N:17])([CH3:15])[CH3:14])(=[O:12])=[O:11])[CH:7]=1.Cl>O1CCOCC1>[NH2:17][C:16]1[C:13]([CH3:15])([CH3:14])[S:10](=[O:12])(=[O:11])[CH2:9][C@@:8]([C:6]2[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=2[F:27])([CH2:18][F:19])[N:20]=1.[NH2:17][C:16]1[C:13]([CH3:15])([CH3:14])[S:10](=[O:12])(=[O:11])[CH2:9][C@:8]([C:6]2[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=2[F:27])([CH2:18][F:19])[N:20]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 86715724HCID 86715724, compound

Product 2

HCID 86715851HCID 86715851, compoundYield 73%HCID 86728107HCID 86728107, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
100 °C

Procedure

To a solution of N-(2-(5-bromo-2-fluorophenyl)-1-((2-cyanopropan-2-yl)sulfonyl)-3-fluoropropan-2-yl)-2-methylpropane-2-sulfinamide (45 g, 93 mmol) in dioxane (800 mL) was added hydrochloric acid, 4.0M solution in 1,4-dioxane (107 mL, 428 mmol). The reaction mixture was heated to 100° C. for 2 d. The reaction was allowed to cool to RT, concentrated, and dried under high vacuum to give a light brown solid. The solids were triturated in DCM, filtered, rinsed, and dried to give a white solid. The compound was separated into its enantiomers via prep-scale supercritical fluid chromatography using a Chiralpak AD-H column with an isocratic 75% carbon dioxide/25% methanol with 0.2% ammonia solvent system to yield (R)-5-amino-3-(5-bromo-2-fluorophenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide (41.4 g, 109 mmol, 78% yield) and (S)-5-amino-3-(5-bromo-2-fluorophenyl)-3-(fluoromethyl)-6,6-dimethyl-3,6-dihydro-2H-1,4-thiazine 1,1-dioxide (38.6 g, 101 mmol, 73%) LC/MS (ESI+) m/z=380.9; 382.9 for both diastereomers. (M+H; 2 bromine isotopes).

Workup

  1. temperatureto cool to RT
  2. concentrationconcentrated
  3. customdried under high vacuum
  4. customto give a light brown solid
  5. customThe solids were triturated in DCM
  6. filtrationfiltered
  7. washrinsed
  8. customdried
  9. customto give a white solid
  10. customThe compound was separated into its enantiomers via prep-scale supercritical fluid chromatography

Sources & evidence

ORD record
ord-7e2c77a2d2ca42b2b8289cd0ce25fcbb
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

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