Triethylamine → (5-Methyl-3-pyrimidin-4-yl-isoxazol-4-yl)-methanol

HRID 83407ノート

反応式

HRID 83407 の反応式
[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][N:8]=2)[C:3]=1[C:13](O)=[O:14].C(N(CC)CC)C.C(OC(Cl)=O)C.[BH4-].[Na+]>C1COCC1.O.[OH-].[Na+]>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][N:8]=2)[C:3]=1[CH2:13][OH:14]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 671578195-Methyl-3-pyrimidin-4-yl-isoxazole-4-carboxylic acid

生成物 1

HCID 67158426(5-Methyl-3-pyrimidin-4-yl-isoxazol-4-yl)-methanol収率 19%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 14798Sodium Hydroxide溶媒

反応条件

温度
-10 °C

実験手順

To a solution of 5-methyl-3-pyrimidin-4-yl-isoxazole-4-carboxylic acid (300 mg, 1.46 mmol) in THF (4 mL) at −10° C. was added triethylamine (203 μL, 1.46 mmol) and then a solution of ethylchloroformate (139 μL, 1.46 mmol) in THF (1 mL) added keeping the temperature below −5° C. After 1 h the mixture was filtered and the filtrate cooled to −10° C. and a suspension of sodiumborohydride (138 mg, 3.66 mmol) in water (1.5 mL) added over 15 minutes keeping the temperature below −5° C. The mixture was then allowed to warm up to room temperature over 2 h and diluted with aqueous sodium hydroxide (1 N) and extracted with ethylacetate. The combined organic layers were then washed with water and brine, dried over sodium sulfate and evaporated. Purification by chromatography (SiO2, dichloromethane:methanol=9:1) afforded the title product (52.5 mg, 19%) which was obtained as white solid. MS: m/e=190.0 [M−H]−.

後処理

  1. customthe temperature below −5° C
  2. filtrationAfter 1 h the mixture was filtered
  3. additionadded over 15 minutes
  4. customthe temperature below −5° C
  5. temperatureto warm up to room temperature over 2 h
  6. extractionextracted with ethylacetate
  7. washThe combined organic layers were then washed with water and brine
  8. dry with materialdried over sodium sulfate
  9. customevaporated
  10. customPurification by chromatography (SiO2, dichloromethane:methanol=9:1)

出典と根拠

ORDレコード
ord-167fa9d9b1024b4abf25d786d97cf02b
出典データセット
uspto-grants-2014_09
特許番号
US08846719B2

反応ノート

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