Methanesulfonyl chloride → HCID 89677168, compound

HRID 2278165Notes

Reaction equation

HRID 2278165 reaction equation
[O:1]1[CH:5]=[C:4]([CH:6]([C:8]2[N:9]=[CH:10][O:11][CH:12]=2)O)[N:3]=[CH:2]1.CCN(C(C)C)C(C)C.CS(Cl)(=O)=O.[N:27]1([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>C(Cl)Cl>[O:1]1[CH:5]=[C:4]([CH:6]([C:8]2[N:9]=[CH:10][O:11][CH:12]=2)[N:30]2[CH2:29][CH2:28][N:27]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:32][CH2:31]2)[N:3]=[CH:2]1

Participants

6

Reactant 4

HCID 31297Methanesulfonyl chloride2×HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 14786620HCID 14786620, compound

Product 1

HCID 89677168HCID 89677168, compoundYield 28.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A round bottom flask was charged with bis(oxazol-4-yl)methanol (200 mg, 1.20 mmol), CH2Cl2 (3 mL), and DIPEA (412 μL, 2.41 mmol). The solution was cooled to 0° C. and MsCl (112 μL, 1.45 mmol) was added dropwise. After stirring 0° C. for 30 min, more MsCl (100 μL, 1.29 mmol) was added. After an additional 30 min at 0° C., the reaction was quenched with brine and extracted with CH2Cl2 (3×). The organics were dried (Na2SO4), filtered, and concentrated under reduced pressure yielding the crude alkyl chloride. The crude intermediate was dissolved in CH2Cl2 (3 mL) and treated with tert-butyl piperazine-1-carboxylate (224 mg, 1.20 mmol) and stirred at room temperature. After 48 h at room temperature, the reaction was quenched with brine and extracted with CH2Cl2 (3×). The organics were dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was chromatographed on a silica gel column (100% CH2Cl2 to 4% MeOH in CH2Cl2) yielding tert-butyl 4-(bis(oxazol-4-yl)methyl)piperazine-1-carboxylate (114 mg, 28%) as a light brown oil. 1H NMR 400 MHz (CDC3) δ 7.87 (s, 2H), 7.69 (s, 2H), 4.78 (s, 1H), 3.45-3.37 (m, 4H), 2.53-2.40 (m, 4H), 1.39 (s, 9H). LCMS (ESI, m/z): 335 [M+H]+.

Workup

  1. waitAfter an additional 30 min at 0° C.
  2. customthe reaction was quenched with brine
  3. extractionextracted with CH2Cl2 (3×)
  4. dry with materialThe organics were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customyielding the crude alkyl chloride
  8. stirringstirred at room temperature
  9. waitAfter 48 h at room temperature
  10. customthe reaction was quenched with brine
  11. extractionextracted with CH2Cl2 (3×)
  12. dry with materialThe organics were dried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customThe residue was chromatographed on a silica gel column (100% CH2Cl2 to 4% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-d8ab1007dbfe4a069deb704f187c84bf
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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