Acetic Acid → HCID 58382495, compound

HRID 1628003Notes

Reaction equation

HRID 1628003 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][N:14]1[C:18]2=[C:19]3[CH:25]=[CH:24][N:23]([S:26]([C:29]4[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=4)(=[O:28])=[O:27])[C:20]3=[N:21][CH:22]=[C:17]2[CH2:16][CH2:15]1.[I:36]I.CC(O)=O.[NH4+].[Cl-]>C1COCC1.O.C([O-])(O)=O.[Na+].C(Cl)Cl>[I:36][C:24]1[N:23]([S:26]([C:29]2[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[C:20]2=[N:21][CH:22]=[C:17]3[CH2:16][CH2:15][N:14]([CH3:13])[C:18]3=[C:19]2[CH:25]=1

Participants

11

Reactant 6

HCID 176Acetic AcidHCID 807IodineHCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 58382087HCID 58382087, compoundHCID 178418339Butyllithium

Product 1

HCID 58382495HCID 58382495, compoundYield 58%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent3×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
20 °C

Procedure

Diisopropylamine (0.29 mL, 2.0 mmol) in THF (5 mL) was cooled to about −70° C. then treated with n-BuLi (1.6 M in hexanes, 1.1 mL, 1.8 mmol) keeping the internal temperature of the reaction at about −60 to −70° C. After about 15 min the mixture was warmed to about 20° C. The mixture was added slowly to the 1-methyl-6-tosyl-1,2,3,6-tetrahydrodipyrrolo[2,3-b:2′,3′-d]pyridine (0.300 g, 0.916 mmol) in THF (5.0 mL) at about −60° C. to −70° C. The mixture was stirred at about −70° C. for about 1 h then iodine (0.27 g, 1.1 mmol) in THF (2 mL) was added keeping the temperature of the mixture at about −65 to −70° C. The mixture was stirred for about 1 h at about −70° C. then AcOH (0.16 mL, 2.8 mmol) and about 1 mL saturated aqueous NH4Cl were added. The mixture was warmed to rt then diluted with water (10 mL), saturated aqueous NaHCO3 (5 mL) and DCM (50 mL). The layers were separated then the aqueous layer was extracted with DCM (15 mL). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated under reduced pressure. The material was triturated in EtOAc (8 mL) then filtered and washed with EtOAc (2 mL) to give the title compound (0.24 g, 58%): LC/MS (Table 2, Method a) Rt=2.52 min; MS m/z 454 (M+H)+.

Workup

  1. customthe internal temperature of the reaction at about −60 to −70° C
  2. customat about −65 to −70° C
  3. stirringThe mixture was stirred for about 1 h at about −70° C.
  4. temperatureThe mixture was warmed to rt
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with DCM (15 mL)
  7. dry with materialThe combined organic layers were dried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe material was triturated in EtOAc (8 mL)
  11. filtrationthen filtered
  12. washwashed with EtOAc (2 mL)

Sources & evidence

ORD record
ord-0a6d2323729342819bbf26fdf4c973c2
Source dataset
uspto-grants-2014_07
Patent number
US08785639B2

Reaction notes

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