Sodium Iodide → 4-[5-(2,4-Difluoro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperidine-1-carboxylic acid benzyl ester

HRID 2288972노트

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HRID 2288972 반응식
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([C:17]2[O:18][C:19]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[F:31])=[C:20]([CH2:22][OH:23])[N:21]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(OS(C)(=O)=O)(=O)=O.C(N(C(C)C)CC)(C)C.[I-].[Na+].[F:52][C:53]([F:57])([F:56])[CH2:54][O-].[Na+]>O1CCCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([C:17]2[O:18][C:19]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[F:31])=[C:20]([CH2:22][O:23][CH2:54][C:53]([F:57])([F:56])[F:52])[N:21]=2)[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 5

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 81560Methanesulfonic anhydrideHCID 23677971Ethanol, 2,2,2-trifluoro-, sodium salt (1:1)HCID 539008614-[5-(2,4-Difluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidine-1-carboxylic acid benzyl ester

생성물 1

HCID 537748754-[5-(2,4-Difluoro-phenyl)-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperidine-1-carboxylic acid benzyl ester

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

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온도
0 °C

실험 절차

To a three neck 0.5 liter round bottom flask fitted with mechanical stirrer, nitrogen inlet and dropping funnel is added 4-[5-(2,4-Difluoro-phenyl)-4-hydroxymethyl-oxazol-2-yl]-piperidine-1-carboxylic acid benzyl ester, methane sulfonic anhydride (5.87 g, 33.7 mmol), and 150 mL of dry tetrahydrofuran. The mixture is stirred and cooled to 0° C., followed by dropwise addition of diisopropyl ethylamine (8.4 mL, 48 mmol). The mixture is stirred for 1 hour at 0° C. and then allowed to warm to room temperature. To the resultant mixture is then added sodium iodide (7.75 g, 51.7 mmol), and the mixture is stirred for an additional three hours. The sodium 2,2,2-trifluoroethoxide (0.151 mmol in 80 mL of dry tetrahydrofuran) is added dropwise over a 15 minute period and the resulting mixture is stirred for an additional 1 hour. The mixture is cooled to 0° C. and carefully quenched with 125 mL of water. After the addition was complete, the mixture is extracted with water and methylene chloride. The aqueous is washed with an additional three portions of methylene chloride, using 300 mL volumes. The organics are combined, washed with brine, dried over magnesium sulfate and concentrated to a thick residue. The residue is purified by preparative medium performance liquid chromatography to give upon concentration the desired fractions of the title compound.

후처리

  1. customTo a three neck 0.5 liter round bottom flask fitted with mechanical stirrer, nitrogen inlet
  2. stirringThe mixture is stirred for 1 hour at 0° C.
  3. temperatureto warm to room temperature
  4. stirringthe resulting mixture is stirred for an additional 1 hour
  5. temperatureThe mixture is cooled to 0° C.
  6. customcarefully quenched with 125 mL of water
  7. additionAfter the addition
  8. extractionthe mixture is extracted with water and methylene chloride
  9. washThe aqueous is washed with an additional three portions of methylene chloride
  10. washwashed with brine
  11. dry with materialdried over magnesium sulfate
  12. concentrationconcentrated to a thick residue
  13. customThe residue is purified by preparative medium performance liquid chromatography

출처 및 근거

ORD 기록
ord-48ededfd2f0648088427b387c4045dc5
출처 데이터셋
uspto-grants-2000_07
특허 번호
US06090825

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