Iodine → tert-butyl 3-((5-tert-butyl-2-iminothiazol-3(2H)-yl)methyl)azetidine-1-carboxylate

HRID 2196814Notes

Reaction equation

HRID 2196814 reaction equation
[CH3:1][C:2]([CH3:7])([CH3:6])[CH2:3][CH:4]=O.[NH2:8][CH2:9][CH:10]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]1.[S-:21][C:22]#[N:23].[K+].II.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>C(#N)C>[C:2]([C:3]1[S:21][C:22](=[NH:23])[N:8]([CH2:9][CH:10]2[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]2)[CH:4]=1)([CH3:7])([CH3:6])[CH3:1]

Participants

7

Reactant 5

HCID 807IodineHCID 763353,3-DimethylbutanalHCID 516872Potassium thiocyanateHCID 656671Sodium PyrosulfiteHCID 10679125Tert-butyl 3-(aminomethyl)azetidine-1-carboxylate

Product 1

HCID 66660694tert-butyl 3-((5-tert-butyl-2-iminothiazol-3(2H)-yl)methyl)azetidine-1-carboxylateYield 72%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 3,3-dimethylbutanal (3.7 mL, 30 mmol), tert-butyl 3-(aminomethyl)azetidine-1-carboxylate (Astatech, 5 g, 27 mmol), and 8 g of 4 Å molecular sieves (8-12 mesh beads) in acetonitrile (50 mL) was stirred at ambient temperature for 72 h. The material was filtered through Celite with acetonitrile (additional 25 mL) then potassium thiocyanate (3.5 g, 35 mmol) was added and the mixture was warmed to 50° C. Iodine (6.8 g, 26.8 mmol) was added and the mixture stirred at 50° C. for 16 h then was cooled to ambient temperature. The mixture was stirred with 75 mL of 20% aqueous sodium metabisulfite for 1 h then the layers were separated and the aqueous layer was extracted with 3×10 mL CH2Cl2. The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure to give the crude title compound (6.3 g, 19 mmol, 72% yield) which was carried on without further purification. MS (DCI/NH3) m/z 326 (M+H)+.

Workup

  1. filtrationThe material was filtered through Celite with acetonitrile (additional 25 mL)
  2. temperaturethe mixture was warmed to 50° C
  3. stirringthe mixture stirred at 50° C. for 16 h
  4. temperaturethen was cooled to ambient temperature
  5. customthe layers were separated
  6. extractionthe aqueous layer was extracted with 3×10 mL CH2Cl2
  7. dry with materialThe combined organics were dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-8ce276200a3545a4a89665e250de5479
Source dataset
uspto-grants-2012_12
Patent number
US08338467B2

Reaction notes

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