Carbon tetrabromide → HCID 118035439, compound

HRID 1775773Notes

Reaction equation

HRID 1775773 reaction equation
[C:1]([O:11]C(C)(C)C)(=[O:10])[CH2:2][C:3]([O:5]C(C)(C)C)=[O:4].C1CCN2C(=NCCC2)CC1.C(Br)(Br)(Br)Br.[Cl-].[NH4+].C([O:38][C:39](/[C:41](=[CH:48]\[C:49](\[CH3:64])=[CH:50]\[CH:51]([CH3:63])[CH2:52][CH:53]([CH3:62])[CH2:54][CH:55]([CH3:61])[CH2:56][CH:57]([CH3:60])[CH2:58][CH3:59])/[CH2:42][CH:43]([CH3:47])[C:44]([OH:46])=[O:45])=[O:40])(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C1COCC1>[C:39](/[C:41](=[CH:48]\[C:49](\[CH3:64])=[CH:50]\[CH:51]([CH3:63])[CH2:52][CH:53]([CH3:62])[CH2:54][CH:55]([CH3:61])[CH2:56][CH:57]([CH3:60])[CH2:58][CH3:59])/[CH2:42][CH:43]([CH3:47])[C:44]([O:46][CH:2]([C:1]([OH:11])=[O:10])[C:3]([OH:5])=[O:4])=[O:45])([OH:38])=[O:40]

Participants

9

Reactant 6

HCID 11205Carbon tetrabromideHCID 11430Potassium CarbonateHCID 25517Ammonium Chloride2×HCID 68324Di-tert-butyl malonateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 118035475HCID 118035475, compound

Product 1

HCID 118035439HCID 118035439, compoundYield 7.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To di-tert-butyl malonate (0.207 mL, 0.925 mmol), THF (40 mL) and DBU (0.139 mL, 0.925) were added, and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was cooled to −20° C., and carbon tetrabromide (207 mg, 0.925 mmol) was added thereto, and the resulting mixture was stirred at −20° C. for 2 hours. To the reaction mixture, a saturated aqueous ammonium chloride solution was added, and the resulting mixture was extracted with chloroform. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. To a portion (80 mg) of the obtained residue, DMF (1.43 mL), Compound 8 (12.5 mg, 0.029 mmol), and potassium carbonate (11.9 mg, 0.086 mmol) were added, and the resulting mixture was stirred at room temperature for 2 hours. To the reaction mixture, a saturated aqueous ammonium chloride solution was added, and the resulting mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by thin-layer chromatography (ethyl acetate/n-hexane=1/9). By using the obtained residue, Compound 22 (1.1 mg) was obtained in the same manner as Step 2 of Example 7.

Workup

  1. temperatureThe reaction mixture was cooled to −20° C.
  2. stirringthe resulting mixture was stirred at −20° C. for 2 hours
  3. extractionthe resulting mixture was extracted with chloroform
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. stirringthe resulting mixture was stirred at room temperature for 2 hours
  7. extractionthe resulting mixture was extracted with ethyl acetate
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe resulting residue was purified by thin-layer chromatography (ethyl acetate/n-hexane=1/9)

Sources & evidence

ORD record
ord-b4945833e3ce4a62b0199b225ed2b8c5
Source dataset
uspto-grants-2016_02
Patent number
US09260459B2

Reaction notes

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