4-Toluenesulfonyl chloride → [3-(2-Hydroxybut-3-yn-2-yl)isoxazol-5-yl]methyl 4-methylbenzenesulfonate

HRID 1398541Notes

Reaction equation

HRID 1398541 reaction equation
[OH:1][CH2:2][C:3]1[O:7][N:6]=[C:5]([C:8]([OH:12])([C:10]#[CH:11])[CH3:9])[CH:4]=1.C(N(CC)CC)C.[C:20]1([CH3:30])[CH:25]=[CH:24][C:23]([S:26](Cl)(=[O:28])=[O:27])=[CH:22][CH:21]=1>C(Cl)Cl>[CH3:30][C:20]1[CH:25]=[CH:24][C:23]([S:26]([O:1][CH2:2][C:3]2[O:7][N:6]=[C:5]([C:8]([OH:12])([C:10]#[CH:11])[CH3:9])[CH:4]=2)(=[O:28])=[O:27])=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 866695832-[5-(Hydroxymethyl)isoxazol-3-yl]but-3-yn-2-ol

Product 1

HCID 86669584[3-(2-Hydroxybut-3-yn-2-yl)isoxazol-5-yl]methyl 4-methylbenzenesulfonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-[5-(hydroxymethyl)isoxazol-3-yl]but-3-yn-2-ol (500 mg, 2.99 mmol) in DCM (5 mL) at 0° C. under an atmosphere of nitrogen was introduced triethylamine (333 mg, 3.29 mmol) and p-toluenesulfonyl chloride (627 mg, 3.29 mmol) in one portion. After warming to RT for 3 hr, the reaction mixture was diluted with DCM (10 mL) and washed with brine (5 mL). The organic extract was dried (Na2SO4), filtered and the filtrate adsorbed onto silica gel in vacuo. Purification by silica gel flash column chromatography (heptane/EtOAc gradient of increasing polarity) furnished the title compound as a colorless oil: 1H NMR (500 MHz, CDCl3) delta 1.84 (3H, s), 2.26 (3H, s), 2.66 (1H, s), 2.86 (1H, br. s), 5.14 (2H, s), 6.41 (1H, s), 7.36 (2H, d, J=8.1 Hz), 7.80 (2H, d, J=8.1 Hz); LC-MS: m/z=+321.9 (M+H)+.

Workup

  1. washwashed with brine (5 mL)
  2. extractionThe organic extract
  3. dry with materialwas dried (Na2SO4)
  4. filtrationfiltered
  5. customPurification
  6. temperatureby silica gel flash column chromatography (heptane/EtOAc gradient of increasing polarity)

Sources & evidence

ORD record
ord-9659975df37248a9a1c4f5da4880c309
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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