Cyclopropanecarboxaldehyde → HCID 90213991, compound

HRID 922529Notes

Reaction equation

HRID 922529 reaction equation
[ClH:1].[NH2:2][C@@H:3]1[CH2:5][C@H:4]1[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:16]=2)=[O:14])=[CH:8][CH:7]=1.[CH:27]1([CH:30]=O)[CH2:29][CH2:28]1.C(=O)([O-])O.[Na+].[BH4-].[Na+]>CO.C1COCC1>[ClH:1].[CH:27]1([CH2:30][NH:2][C@@H:3]2[CH2:5][C@H:4]2[C:6]2[CH:7]=[CH:8][C:9]([NH:12][C:13]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)=[CH:17][CH:16]=3)=[O:14])=[CH:10][CH:11]=2)[CH2:29][CH2:28]1

Participants

7

Reactant 4

HCID 123114CyclopropanecarboxaldehydeHCID 516892Sodium Bicarbonate2×HCID 4311764Sodium borohydrideHCID 86729866HCID 86729866, compound

Product 1

HCID 90213991HCID 90213991, compoundYield 64.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of N-[4-(trans-2-aminocyclopropyl)phenyl]biphenyl-4-carboxamide hydrochloride (2.2 g) in methanol (75 mL)/THF (75 mL) was ice-cooled, and cyclopropanecarbaldehyde (549 mg) and sodium hydrogen carbonate (1.01 g) were added. The mixture was stirred at 60° C. for 1 hr, and ice-cooled to 0° C. and sodium borohydride (456 mg) was added. The mixture was stirred for 1 hr, and saturated aqueous sodium hydrogen carbonate solution was added. The mixture was extracted with ethyl acetate, and the extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate, ethyl acetate/methanol). 10% Hydrochloric acid methanol solution was added and the solvent was evaporated under reduced pressure. The residue was recrystallized from methanol/diisopropyl ether to give the title compound (1.62 g).

Workup

  1. temperaturecooled
  2. temperatureice-cooled to 0° C.
  3. stirringThe mixture was stirred for 1 hr
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe extract was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate, ethyl acetate/methanol)
  9. addition10% Hydrochloric acid methanol solution was added
  10. customthe solvent was evaporated under reduced pressure
  11. customThe residue was recrystallized from methanol/diisopropyl ether

Sources & evidence

ORD record
ord-f78767562e424ec09348e99ed144a00e
Source dataset
uspto-grants-2016_03
Patent number
US09278931B2

Reaction notes

Loading…