Sodium Iodide → 5-(2-{4-[5-(4-Fluoro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperazin-1-yl}-ethyl)-2-methoxy-benzenesulfonamide

HRID 2288998Notes

Reaction equation

HRID 2288998 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][C:11]([N:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:19][O:20][CH2:21][C:22]([F:25])([F:24])[F:23])=[CH:4][CH:3]=1.Cl[CH2:27][CH2:28][C:29]1[CH:30]=[CH:31][C:32]([O:39][CH3:40])=[C:33]([S:35]([NH2:38])(=[O:37])=[O:36])[CH:34]=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]([N:13]3[CH2:18][CH2:17][N:16]([CH2:27][CH2:28][C:29]4[CH:30]=[CH:31][C:32]([O:39][CH3:40])=[C:33]([S:35]([NH2:38])(=[O:36])=[O:37])[CH:34]=4)[CH2:15][CH2:14]3)=[N:10][C:9]=2[CH2:19][O:20][CH2:21][C:22]([F:25])([F:23])[F:24])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 187004001-[5-(4-Fluoro-Phenyl)-4-(2,2,2-Trifluoro-Ethoxymethyl)-Oxazol-2-yl]-PiperazineHCID 187004435-(2-Chloroethyl)-2-methoxy-benzenesulfonamide

Product 1

HCID 187003995-(2-{4-[5-(4-Fluoro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperazin-1-yl}-ethyl)-2-methoxy-benzenesulfonamideYield 58.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 1-[5-(4-fluoro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperazine (0.15 g; 0.42 mmol) in dry dioxane (5 ml) is treated with 5-(2-chloroethyl)-2-methoxy-benzenesulfonamide (0.25 g; 1.0 mmol), sodium iodide (0.15 g; 1.0 mmol) and diisopropylethylamine (0.36 ml; 2.09 mmol) and heated to 100 C. for 16 hours. The reaction mixture is partitioned between ethyl acetate (40 ml) and dilute sodium bicarbonate (20 ml). The aqueous phase is extracted with ethyl acetate (20 ml). The combined organic phases are washed with saturated brine (10 ml), dried over sodium sulfate and concentrated to dryness. Purification by radial chromatography on silica gel using a methanol-ethyl acetate gradient (1%-20%) is followed by a second chromatography using a methanol-dichloromethane gradient (1%-5%). Crystallization from ethyl acetate/hexane affords the product as a white solid (0.14 g; 56%). HNMR (CDCL3): 7.81 (d, 1H, J=2.4 Hz), 7.54 (m, 2H), 7.42 (dd, 1H, J=8.7, 2.0 Hz), 7.14 (t, 2H, J=8.8 Hz), 7.02 (d, 1H, J=8.7 Hz), 5.16 (s, 2H), 4.04 (s, 3H), 4.01 (qt, 2H, J=8.8 Hz), 3.62 (m, 4H), 2.85 (m, 2H), 2.66 (m, 6H).

Workup

  1. temperatureheated to 100 C
  2. customThe reaction mixture is partitioned between ethyl acetate (40 ml) and dilute sodium bicarbonate (20 ml)
  3. extractionThe aqueous phase is extracted with ethyl acetate (20 ml)
  4. washThe combined organic phases are washed with saturated brine (10 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customPurification by radial chromatography on silica gel using a methanol-ethyl acetate gradient (1%-20%)
  8. customCrystallization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-8ae46205882447d2a7fd3c2e38b26233
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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