Diisopropylethylamine → HCID 86589867, compound

HRID 489914Notes

Reaction equation

HRID 489914 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH:20]=[C:19]([C:21](=[O:27])[N:22]([CH2:25][CH3:26])[CH2:23][CH3:24])[CH2:18][CH2:17][CH2:16][CH2:15]2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.C(N(CC)C(C)C)(C)C.[CH:37]1[C:50]2[C:41](=[CH:42][C:43]3[C:48]([C:49]=2C(Cl)=O)=[CH:47][CH:46]=[CH:45][CH:44]=3)[CH:40]=[CH:39][CH:38]=1.ClCCl.CO>CO.[Pd].ClCCl>[CH2:23]([N:22]([CH2:25][CH3:26])[C:21]([CH:19]1[CH2:18][CH2:17][CH2:16][CH2:15][N:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([C:42]3[C:43]4[C:48]([CH:49]=[C:50]5[C:41]=3[CH:40]=[CH:39][CH:38]=[CH:37]5)=[CH:47][CH:46]=[CH:45][CH:44]=4)=[O:7])[CH2:13][CH2:12]2)[CH2:20]1)=[O:27])[CH3:24]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 167528Anthracene-9-carbonyl chloride2×HCID 21226129Dichloromethane methanolHCID 69694095HCID 69694095, compound

Product 1

HCID 86589867HCID 86589867, compoundYield 53.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

4-(6-diethylcarbamoyl-2,3,4,5-tetrahydro-azepin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (30 mg, 0.079 mmol) was dissolved in methanol (20 mL) and 10% palladium on carbon (10% w/w) (˜30 mg) added. The mixture was shaken under a hydrogen atmosphere (50 psi) for 3 h . The catalyst was removed by filtration through Celite® and the solvent evaporated under vacuum. The residue was dissolved in ethyl acetate (10 mL) under nitrogen, cooled to −78° C. and hydrogen chloride was passed in for a few minutes. The solution was allowed to warmed at room temperature then evaporated to dryness overnight in a stream of dry nitrogen. The residue was dissolved in anhydrous dichloromethane (4 mL), N,N-diisopropylethylamine (5 eq, 70 mL) was added followed by a suspension of anthracene-9-carbonyl chloride (Intermediate 3, 0.088 mmol) in dichloromethane (0.175 mL). The thin layer chromatography (9:1 dichloromethane-methanol) showed a new UV spot at Rf 0.40. After 30 minutes, the solution was washed with a mixed sodium hydrogen carbonate/sodium hydroxide solution, dried over anhydrous sodium sulfate, evaporated and the residue purified by chromatography on silica gel eluting with a 1%-2.5%-5%-10% methanol-dichloromethane gradient to give the title compound (20.4 mg, 53%).

Workup

  1. customThe catalyst was removed by filtration through Celite®
  2. customthe solvent evaporated under vacuum
  3. dissolutionThe residue was dissolved in ethyl acetate (10 mL) under nitrogen
  4. customwas passed in for a few minutes
  5. temperatureto warmed at room temperature
  6. customthen evaporated to dryness overnight in a stream of dry nitrogen
  7. dissolutionThe residue was dissolved in anhydrous dichloromethane (4 mL)
  8. waitAfter 30 minutes
  9. washthe solution was washed with a mixed sodium hydrogen carbonate/sodium hydroxide solution
  10. dry with materialdried over anhydrous sodium sulfate
  11. customevaporated
  12. customthe residue purified by chromatography on silica gel eluting with a 1%-2.5%-5%-10% methanol-dichloromethane gradient

Sources & evidence

ORD record
ord-1670673949e742e4909cbbbe9a7805f6
Source dataset
uspto-grants-2005_12
Patent number
US06979741B2

Reaction notes

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