叔丁醇 → N-BOC-4-氨基噻唑

HRID 46293

反应方程式

HRID 46293 反应方程式
[S:1]1[CH:5]=[C:4](C(O)=O)[N:3]=[CH:2]1.[C:9]([OH:13])([CH3:12])([CH3:11])[CH3:10].C([N:16]([CH2:19]C)CC)C.C1C=CC([O:27]P(OC2C=CC=CC=2)(N=[N+]=[N-])=O)=CC=1>>[C:9]([O:13][C:19](=[O:27])[NH:16][C:4]1[N:3]=[CH:2][S:1][CH:5]=1)([CH3:12])([CH3:11])[CH3:10]

参与物

5

反应物 4

HCID 6386叔丁醇HCID 8471三乙胺HCID 123414叠氮磷酸二苯酯HCID 304271噻唑-4-甲酸

产物 1

HCID 53241636N-BOC-4-氨基噻唑收率 64.7%

实验过程

Thiazole-4-carboxylic acid (6.46 g, 50.0 mmol) was slurried in tert-butyl alcohol (280 mL, 2900 mmol). Triethylamine (7.68 mL, 55.1 mmol) and diphenylphosphonic azide (11.9 mL, 55.1 mmol) were added and the reaction was heated at reflux for 18 hours. The reaction was evaporated to a residue. The residue was dissolved in ethyl acetate and washed with water, 5% citric acid (aqueous), water, saturated aqueous sodium bicarbonate and brine. The organic phase was dried over magnesium sulfate and evaporated to a residue. The residue was purified by silica gel chromatography (80 g ISCO™ column, hexanes to ethyl acetate gradient elution). Product fractions were combined and evaporated to a residue. The residue was triturated with 20% methyl t-butyl ether in hexanes. The solid was collected by filtration. Vacuum drying gave 6.48 g of product as a white solid. LCMS Rt=1.46 minutes MS m/z 201 [MH]+

后处理

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 18 hours
  3. customThe reaction was evaporated to a residue
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed with water, 5% citric acid (aqueous), water, saturated aqueous sodium bicarbonate and brine
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. customevaporated to a residue
  8. customThe residue was purified by silica gel chromatography (80 g ISCO™ column, hexanes to ethyl acetate gradient elution)
  9. customevaporated to a residue
  10. customThe residue was triturated with 20% methyl t-butyl ether in hexanes
  11. filtrationThe solid was collected by filtration
  12. customVacuum drying

来源与证据

ORD记录
ord-ca7487c3868f4ad7b197979b3124fb1e
来源数据集
uspto-grants-2013_09
专利号
US08541588B2

关联笔记

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