Sodium Hydroxide → 1-(4-ethylbenzyl)-4-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine

HRID 133592

Reaction equation

HRID 133592 reaction equation
[CH2:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1)[CH3:2].[BH3-]C#N.[Na+].[CH:15]1[C:27]2[CH:26]([CH2:28][O:29][C:30]([NH:32][CH2:33][C:34]([NH:36][CH2:37][CH:38]3[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]3)=[O:35])=[O:31])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[C:19]=2[CH:18]=[CH:17][CH:16]=1.[OH-].[Na+]>ClCCl.C(O)(=O)C.CO>[CH2:1]([C:3]1[CH:10]=[CH:9][C:6]([CH2:7][N:41]2[CH2:42][CH2:43][CH:38]([CH2:37][NH:36][C:34](=[O:35])[CH2:33][NH:32][C:30]([O:29][CH2:28][CH:26]3[C:27]4[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=4[C:20]4[C:25]3=[CH:24][CH:23]=[CH:22][CH:21]=4)=[O:31])[CH2:39][CH2:40]2)=[CH:5][CH:4]=1)[CH3:2]

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 208614-EthylbenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 543594714-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine

Product 1

HCID 692145361-(4-ethylbenzyl)-4-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 10129899Acetic acid methanolSolvent

Conditions

Temperature
60 °C

Procedure

4-Ethylbenzaldehyde (1.09 g, 8.16 mmol) and NaBH3CN (6.59 g, 10.5 mmol) were added to a 2.5% acetic acid/methanol (80 mL) solution of 4-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine (1.00 g, 2.33 mmol). The resulting reaction mixture was stirred at 60° C. for 13 hours and cooled to room temperature. A 1 M aqueous solution of NaOH (50 mL) and dichloromethane (50 mL) were then added, and the organic layer was separated. The aqueous layer was extracted with dichloromethane (50 mL×3). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The obtained crude product was purified by column chromatography (SiO2, methanol/ethyl acetate=2:8) to thereby provide 1-(4-ethylbenzyl)-4-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine (740 mg, 62%).

Workup

  1. customThe resulting reaction mixture
  2. temperaturecooled to room temperature
  3. customthe organic layer was separated
  4. extractionThe aqueous layer was extracted with dichloromethane (50 mL×3)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe obtained crude product
  10. customwas purified by column chromatography (SiO2, methanol/ethyl acetate=2:8) to thereby provide 1-(4-ethylbenzyl)-4-[[N-(9-fluorenylmethyloxycarbonyl)glycyl]aminomethyl]piperidine (740 mg, 62%)

Sources & evidence

ORD record
ord-baf500ccb99b4285b72dee06f08f4ee7
Source dataset
uspto-grants-2008_06
Patent number
US07390830B1

Linked notes

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