tert-Butanol → tert-butyl N-(1,3-thiazol-4-yl)carbamate

HRID 1401959Notes

Reaction equation

HRID 1401959 reaction equation
[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]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 123414Diphenylphosphoryl azideHCID 3042714-Thiazolecarboxylic acid

Product 1

HCID 53241636tert-butyl N-(1,3-thiazol-4-yl)carbamateYield 64.7%

Procedure

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]+

Workup

  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

Sources & evidence

ORD record
ord-86ace10e3a424a9cb2ef335647e39750
Source dataset
uspto-grants-2014_12
Patent number
US08907101B2

Reaction notes

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