Hydrochloric Acid → HCID 86732272, compound

HRID 930435Notes

Reaction equation

HRID 930435 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@@:9]([NH:18][S@@](C(C)(C)C)=O)([CH2:11][C@H:12]([OH:17])[C:13]([F:16])([F:15])[F:14])[CH3:10].Cl.O1CCOCC1.[C:32]([N:40]=[C:41]=S)(=[O:39])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>C(Cl)Cl.CO>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C@:9]1([CH3:10])[CH2:11][C@@H:12]([C:13]([F:14])([F:15])[F:16])[O:17][C:41]([NH:40][C:32](=[O:39])[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[N:18]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 312751,4-DioxaneHCID 68284Benzoyl isothiocyanateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86732271HCID 86732271, compound

Product 1

HCID 86732272HCID 86732272, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of (R)-N-((2S,4S)-2-(2-chloro-3-fluorophenyl)-5,5,5-trifluoro-4-hydroxypentan-2-yl)-2-methylpropane-2-sulfinamide (1.75 g, 4.49 mmol) in DCM (10 mL) and methanol (5.00 mL) was added hydrogen chloride, 4M in 1,4-dioxane (11.22 mL, 44.9 mmol). After 30 min, the mixture was concentrated, diluted with DCM and saturated NaHCO3. The organic layer was washed with brine, dried over sodium sulfate and concentrated in vacuo. This material was dissolved in THF (25 mL) and then treated with benzoyl isothiocyanate (0.695 mL, 5.16 mmol). After 30 min, triethylamine (0.751 mL, 5.39 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.947 g, 4.94 mmol) were added, and the resulted reaction mixture was brought up to 70° C. for 40 min. The reaction mixture was partitioned between EtOAc and water. The separated organic layer was washed with brine, dried over sodium sulfate and filtered. The filtrate was concentrated in vacuo and the crude was purified by silica gel column (40 g, 0-40% EtOAc/hexane in 25 min) to afford N-((4S,6S)-4-(2-chloro-3-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)benzamide as an off-white solid (1.73 g, 93% yield). MS m/z=415 [M+H]+. Calculated for C19H15ClF4N2O2: 414.8.

Workup

  1. concentrationthe mixture was concentrated
  2. additiondiluted with DCM and saturated NaHCO3
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. dissolutionThis material was dissolved in THF (25 mL)
  7. waitAfter 30 min
  8. customthe resulted reaction mixture
  9. waitwas brought up to 70° C. for 40 min
  10. customThe reaction mixture was partitioned between EtOAc and water
  11. washThe separated organic layer was washed with brine
  12. dry with materialdried over sodium sulfate
  13. filtrationfiltered
  14. concentrationThe filtrate was concentrated in vacuo
  15. customthe crude was purified by silica gel column (40 g, 0-40% EtOAc/hexane in 25 min)

Sources & evidence

ORD record
ord-1076f8134a0245ac9b1fb9afa854270e
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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