Sulfuryl chloride → HCID 68998780, compound

HRID 1909659Notes

Reaction equation

HRID 1909659 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[CH:23]=[CH:22][C:10]([O:11][CH2:12][C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[CH2:18][CH2:19][CH2:20][NH2:21])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1.[CH:26](N(C(C)C)CC)(C)C.[S:35](Cl)(Cl)(=[O:37])=[O:36]>ClCCl>[ClH:1].[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[CH:23]=[CH:22][C:10]([O:11][CH2:12][C@@H:13]3[CH2:17][CH2:16][CH2:15][N:14]3[CH2:18][CH2:19][CH2:20][NH:21][S:35]([CH3:26])(=[O:37])=[O:36])=[CH:9][CH:8]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 24648Sulfuryl chlorideHCID 81531DiisopropylethylamineHCID 68998070HCID 68998070, compound

Product 1

HCID 68998780HCID 68998780, compoundYield 14.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

3-{(S)-2-[4-(4-Chloro-phenoxy)-phenoxymethyl]-pyrrolidin-1-yl}-propylamine (50 mg, 0.139 mmol) and Diisopropylethyl amine (26.9 mg, 0.208 mmol) were taken into dichloromethane (2 ml). The reaction was cooled to −10° C. and the sulfonyl chloride (0.013 mL, 0.166 mmol) was added dropwise over 5 minutes. The reaction was left to slowly warm to room temperature for 24 h. The mixture was then partitioned between sodium bicarbonate (aq) and dichloromethane. The aqueous layer was washed with dichloromethane (3×). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated to dryness. The crude compound was purified by flash silica chromatography (40:1 silica ratio, eluted with 2% methanol in dichloromethane, 5% methanol in dichloromethane, and 10% methanol in dichloromethane). The pure product was then taken into 4M HCl in dioxane and left to react at room temperature for 3 h. The mixture was concentrated to dryness under vacuum to yield the title product (5.2 mg, 0.01 mmol, 7.8%); LCMS; m/z 439 (m of free amine); 1H NMR (400 MHz, DMSO-d6) 1.80-1.88 (m, 1H), 1.92-1.97 (m, 3H), 2.02-2.10 (m, 1H), 2.20-2.27 (m, 1H), 3.03 (s, 3H), 3.05-3.14 (m, 2H), 3.15-3.32 (m, 2H), 3.45-3.51 (m, 2H), 3.64-3.72 (m, 1H), 4.205-4.33 (m, 2H), 6.93-6.95 (m, 2H), 7.07 (s, 4H), 7.39-7.41 (m, 2H).

Workup

  1. waitThe reaction was left
  2. temperatureto slowly warm to room temperature for 24 h
  3. customThe mixture was then partitioned between sodium bicarbonate (aq) and dichloromethane
  4. washThe aqueous layer was washed with dichloromethane (3×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated to dryness
  8. customThe crude compound was purified by flash silica chromatography (40:1 silica ratio, eluted with 2% methanol in dichloromethane, 5% methanol in dichloromethane, and 10% methanol in dichloromethane)
  9. waitleft
  10. customto react at room temperature for 3 h
  11. concentrationThe mixture was concentrated to dryness under vacuum

Sources & evidence

ORD record
ord-91ad814525154d3a9da03565ec239242
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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