2,6-Lutidine → Ethyl 2-amino-4-(3-bromophenyl)-4-methyl-5,6-dihydro-4H-1,3-thiazine-6-carboxylate

HRID 1992293Notes

Reaction equation

HRID 1992293 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:8](=[CH2:17])[CH2:9][CH:10](O)[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[CH:6][CH:7]=1.N1C(C)=CC=CC=1C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[NH2:41][C:42]([NH2:44])=[S:43]>C(#N)C>[NH2:44][C:42]1[S:43][CH:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH2:9][C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=2)([CH3:17])[N:41]=1

Participants

6

Reactant 4

HCID 79372,6-LutidineHCID 67749Trifluoromethanesulfonic anhydrideHCID 2723790ThioureaHCID 57948922HCID 57948922, compound

Product 1

HCID 57948958Ethyl 2-amino-4-(3-bromophenyl)-4-methyl-5,6-dihydro-4H-1,3-thiazine-6-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of ethyl 4-(3-bromophenyl)-2-hydroxypent-4-enoate (5.1 g, 17 mmoles) in acetonitrile (68 mL) is added 2,6-lutidine (2.19 g, 20.4 mmol, 1.2 equiv). The reaction is cooled to 0° C. and trifluoromethanesulfonic anhydride (3.30 mL, 19.6 mmol, 1.15 equiv) is added dropwise over approximately 5 minutes. The mixture is stirred at 0° C. for 20 minutes. Thiourea (2.59 g, 34.0 mmol, 2 equiv) is added and the reaction is warmed to room temperature. After 45 minutes, the mixture is concentrated under reduced pressure. The resulting viscous orange oil is then added via large pipette to stirring sulfuric acid (17.8 M, 8 mL) at room temperature. After 20 minutes, the mixture is added dropwise to a vigorously stirring, 0° C. solution of K2CO3 (ca. 50 g) in 50 mL H2O). Additional water is added to enable stirring upon solid formation during the quench. The tan/orange solid is collected by filtration. The solid is allowed to dry on the filter paper by a stream of air for 1 h to give the title compound as a mixture of diastereomers which is used without further purification: MS (m/z): 357, 359 (M+1).

Workup

  1. temperaturethe reaction is warmed to room temperature
  2. waitAfter 45 minutes
  3. concentrationthe mixture is concentrated under reduced pressure
  4. additionThe resulting viscous orange oil is then added via large pipette
  5. stirringto stirring sulfuric acid (17.8 M, 8 mL) at room temperature
  6. waitAfter 20 minutes
  7. additionthe mixture is added dropwise to
  8. stirringa vigorously stirring, 0° C. solution of K2CO3 (ca. 50 g) in 50 mL H2O)
  9. additionAdditional water is added
  10. stirringto enable stirring upon solid formation during the quench
  11. filtrationThe tan/orange solid is collected by filtration
  12. customto dry on the filter paper by a stream of air for 1 h

Sources & evidence

ORD record
ord-f7251767e65b411aa9a854a487016682
Source dataset
uspto-grants-2010_01
Patent number
US07648983B2

Reaction notes

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