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

HRID 332010노트

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HRID 332010 반응식
[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]

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회HCID 14798Sodium Hydroxide용매

반응 조건

온도
-10 °C

실험 절차

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]−.

후처리

  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)

출처 및 근거

ORD 기록
ord-8cb6e1ce2b74468dbde0bc7bd14a980c
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08877782B2

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