Dichloromethane → HCID 86631907, compound

HRID 1691984Notes

Reaction equation

HRID 1691984 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]2[N:6]=[C:7]([N:9]3[CH2:14][CH2:13][CH2:12][C@H:11]([OH:15])[CH2:10]3)[S:8][C:4]=2[CH:3]=1.ClCCl.C(N(CC)CC)C.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(OCC)C>[CH3:28][S:29]([O:15][C@H:11]1[CH2:12][CH2:13][CH2:14][N:9]([C:7]2[S:8][C:4]3[CH:3]=[C:2]([Br:1])[CH:17]=[CH:16][C:5]=3[N:6]=2)[CH2:10]1)(=[O:31])=[O:30]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 66906271HCID 66906271, compound

Product 1

HCID 86631907HCID 86631907, compound

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

In a 20 mL scintillation vial equipped with a magnetic stirbar was added (S)-1-(6-bromobenzo[d]thiazol-2-yl)piperidin-3-ol (Reference Example 7, 1.15 g, 3.67 mmol). Dichloromethane (10 mL) was then added to the reaction vial to give a solution. To this stirred solution was added 2.5 equivalents of triethylamine (1.279 mL, 9.18 mmol). The reaction vial was capped with a septum and vented to a bubbler. The vial was placed in an ice water bath. To this stirred, 0° C. solution was added dropwise 2.0 equivalents of methanesulfonyl chloride (0.572 mL, 7.34 mmol). The reaction mixture was stirred for 10 minutes at 0° C., then the ice bath was removed and stirring was continued at room temperature overnight. The reaction mixture was washed with water, then dried (MgSO4) and filtered. The filtrate was concentrated under reduced pressure to give an oil that was purified by column chromatography on an Analogix IntelliFlash-280 (Analogix SF10-4g [2 connected in series], 100% dichloromethane). Fractions containing product were combined and concentrated under reduced pressure to give a solid that was treated with diethyl ether. This suspension was filtered to collect (S)-1-(6-bromobenzo[d]thiazol-2-yl)piperidin-3-yl methanesulfonate. 1H NMR (300 MHz, CDCl3) δ ppm 1.68-1.81 (m, 1H), 1.94-2.16 (m, 3H), 3.06 (s, 3H), 3.51-3.68 (m, 2H), 3.85-3.90 (m, 2H), 4.86-4.93 (m, 1H), 7.37-7.39 (m, 2H), 7.69-7.71 (m, 1H); MS (DCI/NH3) m/z 391 (M+H)+.

Workup

  1. customIn a 20 mL scintillation vial equipped with a magnetic stirbar
  2. customto give a solution
  3. customThe reaction vial was capped with a septum
  4. customThe vial was placed in an ice water bath
  5. customthe ice bath was removed
  6. stirringstirring
  7. waitwas continued at room temperature overnight
  8. washThe reaction mixture was washed with water
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customto give an oil that
  13. customwas purified by column chromatography on an Analogix IntelliFlash-280 (Analogix SF10-4g [2 connected in series], 100% dichloromethane)
  14. additionFractions containing product
  15. concentrationconcentrated under reduced pressure
  16. customto give a solid
  17. filtrationThis suspension was filtered
  18. customto collect (S)-1-(6-bromobenzo[d]thiazol-2-yl)piperidin-3-yl methanesulfonate

Sources & evidence

ORD record
ord-07b7a6164c8b4806a6e83eb03d7c8101
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

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