Hydroxylamine → Cimlanod

HRID 1749190Notes

Reaction equation

HRID 1749190 reaction equation
[NH2:1][OH:2].O.[CH3:4][C:5]1[O:9][C:8]([S:10](Cl)(=[O:12])=[O:11])=[CH:7][CH:6]=1.CCCCCC>C1COCC1.C(OCC)(=O)C>[OH:2][NH:1][S:10]([C:8]1[O:9][C:5]([CH3:4])=[CH:6][CH:7]=1)(=[O:12])=[O:11]

Participants

7

Reactant 4

HCID 787HydroxylamineHCID 962WaterHCID 8058HexaneHCID 178643615-Methylfuran-2-sulfonyl chloride

Product 1

HCID 76685198CimlanodYield 61%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of hydroxylamine (0.92 mL of a 50% aqueous solution; 13.8 mmol) in THF (6 mL) and water (2 mL) cooled to 0° C. was added 5-methylfuran-2-sulfonyl chloride (1 g, 5.5 mmol) as a solution in THF (6 mL) dropwise so as to maintain the temperature below 10° C. The reaction was stirred for 5 minutes, after which time TLC (1:1 hexane:ethyl acetate (H:EA)) showed substantially complete consumption of the sulfonyl chloride. The reaction was diluted twice with 50 mL dichloromethane (DCM) and the organic portion was separated and washed with water (10 mL). The organic portion was dried over sodium sulfate, filtered and concentrated under reduced pressure. The product was chromatographed by silica gel chromatography eluting with heptanes:EtOAc followed by trituration with heptane to provide the title compound as a yellow solid (0.59 g, yield 61%). LC-MS tR=0.91 min; 1H NMR (DMSO, 500 MHz) δ ppm 9.82 (1H, d, J=3.1 Hz), 9.64 (1H, d, J=3.2 Hz), 7.10 (1H, d, J=3.4 Hz), 6.36 (1H, d, J=3.4 Hz), 2.36 (3H, s).

Workup

  1. temperatureto maintain the temperature below 10° C
  2. customconsumption of the sulfonyl chloride
  3. additionThe reaction was diluted twice with 50 mL dichloromethane (DCM)
  4. customthe organic portion was separated
  5. washwashed with water (10 mL)
  6. dry with materialThe organic portion was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe product was chromatographed by silica gel chromatography
  10. washeluting with heptanes

Sources & evidence

ORD record
ord-b184672adac24602a6330ec3ad8df96d
Source dataset
uspto-grants-2015_10
Patent number
US09156804B2

Reaction notes

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