Triethylamine → 4-(5-Bromo-2,3-dihydrobenzofuran-2-yl)-1-(propylsulfonyl)piperidine

HRID 1025505Notes

Reaction equation

HRID 1025505 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)[CH2:7][C:6]=2[CH:16]=1.CCN(CC)CC.[CH2:24]([S:27](Cl)(=[O:29])=[O:28])[CH2:25][CH3:26]>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][CH:8]([CH:10]3[CH2:11][CH2:12][N:13]([S:27]([CH2:24][CH2:25][CH3:26])(=[O:29])=[O:28])[CH2:14][CH2:15]3)[CH2:7][C:6]=2[CH:16]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 662791-Propanesulfonyl chlorideHCID 674691344-(5-Bromo-2,3-dihydrobenzofuran-2-yl)piperidine2×

Product 1

HCID 674689334-(5-Bromo-2,3-dihydrobenzofuran-2-yl)-1-(propylsulfonyl)piperidineYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-(5-bromo-2,3-dihydrobenzofuran-2-yl)piperidine (Compound 9A, 185 mg, 0.656 mmol) and Et3N (0.18 mL, 1.311 mmol) in CH2Cl2 (6 mL) at 0° C. was added propane-1-sulfonyl chloride (140 mg, 0.983 mmol). Upon completion of addition, the reaction mixture was warmed to room temperature, where it stirred for 2 hours. After this time, the reaction mixture was diluted with CH2Cl2 (5 mL) and washed with aqueous NaHCO3 (saturated, 5 mL). The organic layer was separated, dried (Na2SO4), filtered, and concentrated to yield a residue. The residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 0 to 50% EtOAc) to afford Compound 10A as a white solid (213 mg, 0.549 mmol, 84% yield). 1H NMR (500 MHz, CDCl3) δ ppm 7.27-7.25 (m, 1 H), 7.21 (dd, J=8.4, 2.1 Hz, 1 H), 6.63 (d, J=8.3 Hz, 1 H), 4.63-4.53 (m, 1 H), 3.93-3.84 (m, 2 H), 3.22 (dd, J=15.7, 9.1 Hz, 1 H), 2.96 (dd, J=15.8, 8.1 Hz, 1 H), 2.91-2.86 (m, 2 H), 2.80-2.71 (m, 2 H), 2.05-1.99 (m, 1 H), 1.90-1.81 (m, 2 H), 1.80-1.71 (m, 2 H), 1.53-1.41 (m, 2 H), 1.07 (t, J=7.4 Hz, 3 H). LC/MS (m/z)=389 (M+H)+.

Workup

  1. additionUpon completion of addition
  2. washwashed with aqueous NaHCO3 (saturated, 5 mL)
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield a residue
  8. customThe residue was purified by column chromatography (silica gel, hexanes/EtOAc gradient 0 to 50% EtOAc)

Sources & evidence

ORD record
ord-795a9f80bb654060b7cf70921c84b491
Source dataset
uspto-grants-2014_05
Patent number
US08729084B2

Reaction notes

Loading…