Isopropyl chloroformate → [5-Cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol

HRID 2423421ノート

反応式

HRID 2423421 の反応式
[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:15]([Cl:16])=[CH:14][N:13]=[CH:12][C:11]=3[Cl:17])[C:6]=2[C:18](O)=[O:19])[CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.ClC(OC(C)C)=O.[BH4-].[Na+]>C1COCC1.O>[CH:1]1([C:5]2[O:9][N:8]=[C:7]([C:10]3[C:11]([Cl:17])=[CH:12][N:13]=[CH:14][C:15]=3[Cl:16])[C:6]=2[CH2:18][OH:19])[CH2:2][CH2:3][CH2:4]1

参加物

7

反応物 4

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 4311764Sodium borohydrideHCID 593214695-Cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylic acid

生成物 1

HCID 59321566[5-Cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol収率 62%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of 5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolecarboxylic acid (808 mg, 2.59 mmol) in THF (13 mL) at 0° C. was added triethylamine (0.361 mL, 2.59 mmol) followed by isopropyl chloroformate (1 M in toluene, 2.59 mL, 2.59 mmol). The solution was stirred at 0° C. for approximately 1 hour and then was filtered into a solution of sodium borohydride (127 mg, 3.37 mmol) in water (1 mL) at 0° C. The solution was allowed to warm to ambient temperature and was then concentrated. Water was added and the mixture was extracted three times with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, concentrated and purified by chromatography (silica gel, 0-40% ethyl acetate in hexanes gradient elution) to afford [5-cyclobutyl-3-(3,5-dichloro-4-pyridinyl)-4-isoxazolyl]methanol (478 mg, 62%). 1H-NMR (400 MHz, DMSO-d6) δ 8.79 (s, 2H), 4.97-4.94 (m, 1H), 4.16-4.15 (m, 2H), 3.92-3.83 (m, 1H), 2.40-2.30 (m, 4H), 2.10-2.01 (m, 1H), 1.99-1.89 (m, 1H).

後処理

  1. temperatureto warm to ambient temperature
  2. concentrationwas then concentrated
  3. additionWater was added
  4. extractionthe mixture was extracted three times with ethyl acetate
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated
  8. custompurified by chromatography (silica gel, 0-40% ethyl acetate in hexanes gradient elution)

出典と根拠

ORDレコード
ord-71db0fd2262d4cc5af51692801385486
出典データセット
uspto-grants-2011_06
特許番号
US07960552B2

反応ノート

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