Methyl iodide → HCID 67179855, compound

HRID 2422722Notes

Reaction equation

HRID 2422722 reaction equation
Br[C:2]1[C:3]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[N:4][S:5][C:6]=1[NH:7][C:8]([C@@H:10]1[CH2:12][C@H:11]1[CH3:13])=[O:9].[CH2:20]([Li])CCC.CI>C1COCC1>[CH3:13][C@@H:11]1[CH2:12][C@H:10]1[C:8]([NH:7][C:6]1[S:5][N:4]=[C:3]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:2]=1[CH3:20])=[O:9]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 67180930HCID 67180930, compoundHCID 178418339Butyllithium2×

Product 1

HCID 67179855HCID 67179855, compoundYield 16.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

To (R,R)—N-[4-bromo-3-phenylisothiazol-5-yl]-2-methylcyclopropane-carboxamide (0.50 g, 1.48 mmol) in THF (3 mL), cooled to −78° C., is added 1.1 equivalent n-butyllithium (n-BuLi) (1.6M in hexane, 0.204 mL, 3.26 mmol). Internal temperature is maintained below −68° C. Following addition, the reaction mixture is allowed to stir for 1 h. 1.1 additional equivalents of n-BuLi (1.6M in hexane, 0.204 mL, 3.26 mmol) is then added while keeping the internal temperature below −66° C. After stirring for 2 h, the reaction mixture is warmed to −40° C. for 15 min; and then cooled back down to −78° C. Methyl iodide (0.10 mL, 1.63 mmol) is then added. The reaction mixture is allowed to warm to room temperature and stir over a weekend before the reaction is quenched with satd NH4Cl and diluted with EtOAc. The organic phase is washed with brine, dried (K2CO3) and evaporated. Chromatography over silica gel, eluting with 5-35% EtOAc in hexane, affords (R,R)-2-methyl-N-(4-methyl-3-phenylisothiazol-5-yl)-cyclopropanecarboxamide. Yield: 16.4%. ES-MS: 273.2 (m+1).

Workup

  1. temperatureInternal temperature is maintained below −68° C
  2. additionaddition
  3. customthe internal temperature below −66° C
  4. stirringAfter stirring for 2 h
  5. temperatureand then cooled back down to −78° C
  6. temperatureto warm to room temperature
  7. stirringstir over a weekend before the reaction
  8. customis quenched with satd NH4Cl
  9. additiondiluted with EtOAc
  10. washThe organic phase is washed with brine
  11. dry with materialdried (K2CO3)
  12. customevaporated
  13. washChromatography over silica gel, eluting with 5-35% EtOAc in hexane

Sources & evidence

ORD record
ord-1e7258abb7494bc3919ad5a1df228e43
Source dataset
uspto-grants-2011_06
Patent number
US07960419B2

Reaction notes

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