N-Boc thiourea → Tert-butyl 4-(methylthio)thiazol-2-ylcarbamate

HRID 1620875Notes

Reaction equation

HRID 1620875 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]([NH2:11])=[S:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:13][C:14](=O)[S:15][CH3:16]>C(O)C>[CH3:16][S:15][C:14]1[N:11]=[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[S:10][CH:13]=1

Participants

4

Reactant 2

HCID 4095660N-Boc thioureaHCID 13272135S-Methyl bromoethanethioate

Product 1

HCID 57571883Tert-butyl 4-(methylthio)thiazol-2-ylcarbamateYield 50%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

N-tert-butoxycarbonylthiourea (503, 0.841 g, 4.77 mmol, prepared according to Schiavi, B.; Ahond, A.; Poupat, C.; Potier, P. Synth. Commun. 2002, 32, 1671) was suspended in ethanol (7.0 mL) and cooled in an ice bath. A solution of S-methyl bromoethanethioate (1.371 g, 5.0582 mmol, prepared according to Praveen Rao, P. N.; Amini, M.; Li, H.; Habeeb, A. G.; Knaus, E. E. J. Med. Chem. 2003, 46, 4872-82) in ethanol (7.0 mL) was added dropwise over 3 minutes. The suspension turned homogeneous at the end of the addition, the bath was removed, and the reaction was stirred at room temperature. The solvent was removed, and the crude material was partitioned between dichloromethane and water. The organics were washed with water and brine. The combined aqueous layers were back-extracted with dichloromethane, and the combined organics were dried with anhydrous MgSO4, filtered, and concentrated in vacuo to an orange glass (stench). The crude material was adsorbed onto ca. 5 g silica gel with ethyl acetate, and flushed through a plug of silica gel with hexanes (discarded) followed by 9:1 hexanes:ethyl acetate. The eluent was evaporated in vacuo to yield 504 (589 mg, 50%) as a colorless solid.

Workup

  1. temperaturecooled in an ice bath
  2. additionThe suspension turned homogeneous at the end of the addition
  3. customthe bath was removed
  4. customThe solvent was removed
  5. customthe crude material was partitioned between dichloromethane and water
  6. washThe organics were washed with water and brine
  7. extractionThe combined aqueous layers were back-extracted with dichloromethane
  8. dry with materialthe combined organics were dried with anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to an orange glass (stench)
  11. customflushed through a plug of silica gel with hexanes (discarded)
  12. customThe eluent was evaporated in vacuo

Sources & evidence

ORD record
ord-6c1b89e340a547d690318fe8f948605e
Source dataset
uspto-grants-2014_07
Patent number
US08772502B2

Reaction notes

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