Ethyl Bromide → Ethyl Bromide

HRID 2201979Notes

Reaction equation

HRID 2201979 reaction equation
[Mg].[CH2:2]([Br:4])[CH3:3].[Cl:5][C:6]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[C:7]=1[NH2:8].[C:14]([O:18][C:19]([NH:21][C:22]1[S:23][C:24]([C:27](OCC)=[O:28])=[CH:25][N:26]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15].[Cl-].[NH4+]>O1CCCC1.II.C(OCC)(=O)C>[CH2:2]([Br:4])[CH3:3].[Cl:5][C:6]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[C:7]=1[NH:8][C:27]([C:24]1[S:23][C:22]([NH:21][C:19](=[O:20])[O:18][C:14]([CH3:16])([CH3:15])[CH3:17])=[N:26][CH:25]=1)=[O:28]

Participants

10

Reactant 5

HCID 6332Ethyl BromideHCID 68972-Chloro-6-methylanilineHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 7213140Ethyl 2-((tert-butoxy(hydroxy)methylidene)amino)-1,3-thiazole-5-carboxylate

Product 2

HCID 6332Ethyl BromideHCID 18184791Tert-butyl (5-((2-chloro-6-methylphenyl)carbamoyl)thiazol-2-YL)carbamate

Reagents, catalysts & solvents 3

HCID 807IodineCatalystHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Magnesium turnings (3.87 g) were charged into a round bottom flask. Tetrahydrofuran (15 mL) was added to the flask. Iodine (30 mg) was added. A solution of ethyl bromide (16 g in 60 mL tetrahydrofuran) was prepared and 10 mL of this solution was slowly charged to the round bottom flask. The reaction mixture was stirred at 20° C. to 25° C. for 5 minutes and the remaining amount of ethyl bromide was added slowly over 30 minutes. The reaction mixture was heated to gentle reflux for 30 minutes and was cooled to −5° C. to −10° C. 2-Chloro-6-methylaniline (22.86 g) was added drop-wise at −5° C. to −10° C. and the temperature of the reaction mixture was slowly raised to 15° C. to 20° C. Ethyl 2-[(tert-butoxycarbonyl)amino]-1,3-thiazole-5-carboxylate (10 g) dissolved in tetrahydrofuran (60 mL) was slowly added to the reaction mixture over 30 minutes. The reaction mixture was stirred for 3 hours. The reaction mixture was poured slowly into 25% ammonium chloride solution (100 mL) with stirring. Ethyl acetate (100 mL) was added and stirred for 30 minutes, filtered, suck dried, and dried under vacuum at 40° C. to 45° C. to obtain the title compound.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto gentle reflux for 30 minutes
  3. temperaturewas cooled to −5° C. to −10° C
  4. temperaturethe temperature of the reaction mixture was slowly raised to 15° C. to 20° C
  5. additionwas slowly added to the reaction mixture over 30 minutes
  6. stirringThe reaction mixture was stirred for 3 hours
  7. stirringwith stirring
  8. stirringstirred for 30 minutes
  9. filtrationfiltered
  10. customsuck dried
  11. customdried under vacuum at 40° C. to 45° C.

Sources & evidence

ORD record
ord-57e322c802574613a79771428f551118
Source dataset
uspto-grants-2016_06
Patent number
US09365526B2

Reaction notes

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