Hydrochloric Acid → HCID 67324574, compound

HRID 2365446Notes

Reaction equation

HRID 2365446 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1C(OC(C)(C)C)=O.C(N(CC)C(C)C)(C)C.[F:24][CH:25]([F:37])[O:26][C:27]1[CH:32]=[CH:31][C:30]([S:33]([Cl:36])(=[O:35])=[O:34])=[CH:29][CH:28]=1.Cl>C(Cl)Cl.O1CCOCC1>[ClH:36].[F:37][CH:25]([F:24])[O:26][C:27]1[CH:28]=[CH:29][C:30]([S:33]([N:6]2[CH2:5][CH2:4][NH:3][C@@H:2]([CH3:1])[CH2:7]2)(=[O:35])=[O:34])=[CH:31][CH:32]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 81531DiisopropylethylamineHCID 27782234-(Difluoromethoxy)benzenesulfonyl chlorideHCID 10081508tert-Butyl (2S)-2-methylpiperazine-1-carboxylate

Product 1

HCID 67324574HCID 67324574, compoundYield 95.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (1.5 g, 7.49 mmol, supplier Aldrich) and N,N-diisopropylethylamine (1.962 mL, 11.23 mmol) in dry DCM (20 mL) was added 4-[(difluoromethyl)oxy]benzenesulfonyl chloride (1.253 mL, 7.86 mmol, supplier Aldrich) dropwise. The solution was stirred at room temperature for 4 h and then left to stand for 16 h. The solution was washed with aqueous sodium bicarbonate (20 mL), 0.5 M HCl (20 mL) and brine (20 mL) before the organic phase was isolated by phase separator. To the solution was added hydrochloric acid (1.872 mL, 7.49 mmol) 4M in dioxane and the reaction stirred at room temperature for 3 h. LCMS showed only partial reaction, so further hydrochloric acid (1.872 mL, 7.49 mmol) 4M in dioxane was added and the reaction stirred for 21 h. The reaction mixture was then concentrated under vacuum to give the title compound (2.448 g) as a pale yellow solid.

Workup

  1. waitleft
  2. waitto stand for 16 h
  3. washThe solution was washed with aqueous sodium bicarbonate (20 mL), 0.5 M HCl (20 mL) and brine (20 mL) before the organic phase
  4. customwas isolated by phase separator
  5. stirringthe reaction stirred at room temperature for 3 h
  6. customreaction
  7. stirringthe reaction stirred for 21 h
  8. concentrationThe reaction mixture was then concentrated under vacuum

Sources & evidence

ORD record
ord-61074b01a66b410dbd292c9f8b60e49c
Source dataset
uspto-grants-2014_04
Patent number
US08697703B2

Reaction notes

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