Sodium Iodide → 5-(2-{4-[5-(4-Fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-hydroxy-benzenesulfonamide

HRID 2288996Notes

Reaction equation

HRID 2288996 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:19][OH:20])=[CH:4][CH:3]=1.Cl[CH2:22][CH2:23][C:24]1[CH:25]=[CH:26][C:27]([OH:34])=[C:28]([S:30]([NH2:33])(=[O:32])=[O:31])[CH:29]=1.[I-].[Na+].C(N(C(C)C)CC)(C)C>O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([CH:13]3[CH2:14][CH2:15][N:16]([CH2:22][CH2:23][C:24]4[CH:25]=[CH:26][C:27]([OH:34])=[C:28]([S:30]([NH2:33])(=[O:31])=[O:32])[CH:29]=4)[CH2:17][CH2:18]3)=[N:10][C:9]=2[CH2:19][OH:20])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 187004285-(2-Chloroethyl)-2-hydroxy-benzenesulfonamideHCID 18700441[5-(4-Fluoro-Phenyl)-2-Piperidin-4-yl-Oxazol-4-yl]Methanol

Product 1

HCID 187004715-(2-{4-[5-(4-Fluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidin-1-yl}-ethyl)-2-hydroxy-benzenesulfonamideYield 16.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of [5-(4-fluoro-phenyl)-2-piperidin-4-yl-oxazol-4-yl]methanol (0.20 g; 0.72 mmol) in dry dioxane (6 ml) is treated with 5-(2-chloroethyl)-2-hydroxy-benzenesulfonamide (0.36 g; 1.45 mmol), sodium iodide (0.22 g; 1.45 mmol) and diisopropylethylamine (0.50 ml; 2.88 mmol) and heated to 100 C. for 16 hours. The reaction is cooled and partitioned between ethyl acetate (30 ml) and water (10 ml). The aqueous phase is washed with ethyl acetate (2×15 ml), dried over sodium sulfate and concentrated to dryness. Purification by radial chromatography using a methanol/ethyl acetate gradient (5%-40%) is followed by a second chromatography using a methanol/dichloromethane gradient (5%-30%). Crystallization from methanol/ethyl acetate afforded the product as a white solid (0.055 g; 16%). HNMR (CD3OD): 7.75 (m, 2H), 7.64 (d, 1H, J=2.1 Hz), 7.31 (dd, 1H, J=8.4; 2.1 Hz), 7.23 (t, 2H, J=8.8 Hz), 6.92 (d, 1H, J=8.4 Hz), 4.63 (s, 2H), 3.12 (m, 2H), 2.96 (m, 1H), 2.82 (m, 2H), 2.66 (m, 2H), 2.34 (m, 2H), 2.17 (m, 2H), 1.99 (m, 2H). Mass spectrum: m/e calculated (MH+)=476.6; observed (MH+)=476.2.

Workup

  1. temperatureheated to 100 C
  2. temperatureThe reaction is cooled
  3. custompartitioned between ethyl acetate (30 ml) and water (10 ml)
  4. washThe aqueous phase is washed with ethyl acetate (2×15 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customPurification by radial chromatography
  8. customCrystallization from methanol/ethyl acetate

Sources & evidence

ORD record
ord-f8940c635d42446c953263185b91254f
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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