1-Boc-4-(aminomethyl)piperidine → 4-[(7-Nitro-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 983454Notes

Reaction equation

HRID 983454 reaction equation
[N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][C:10](=O)[CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([CH2:28][NH2:29])[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CO.C(Cl)Cl>ClC(Cl)C>[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([CH2:28][NH:29][CH:10]2[CH2:9][CH2:8][C:7]3[C:12](=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH2:11]2)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 7368171-Boc-4-(aminomethyl)piperidineHCID 5049666Sodium triacetoxyborohydrideHCID 113214437-Nitro-2-tetraloneHCID 21226129Dichloromethane methanol

Product 1

HCID 112922004-[(7-Nitro-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 7-nitro-3,4-dihydro-1H-naphthalen-2-one (600 mg, 2.98 mmol), prepared as described in J. Med. Chem., 1989, 32(9), 2128-34, and 4-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (700 mg, 3.3 mmol) in dichloroethane (50 mL) under a nitrogen atmosphere was added sodium triacetoxyborohydride (1.4 g, 6.5 mmol, 2 eq.) in a single portion. The reaction was stirred at room temperature for 24 h. The reaction was concentrated in vacuo and partitioned between EtOAc (100 mL) and 5% aq. KOH (50 mL). The aqueous layer was extracted twice more with EtOAc (2×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated to afford a dark oil. Flash chromatography on silica gel eluting with 5% methanol/methylene chloride afforded 4-[(7-nitro-1,2,3,4-tetrahydro-naphthalen-2-ylamino)-methyl]-piperidine-1-carboxylic acid tert-butyl ester, as an oil (790 mg).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. custompartitioned between EtOAc (100 mL) and 5% aq. KOH (50 mL)
  3. extractionThe aqueous layer was extracted twice more with EtOAc (2×50 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a dark oil

Sources & evidence

ORD record
ord-b04c96267dc24f0ca25957e8b05d726e
Source dataset
uspto-grants-2005_03
Patent number
US06864266B2

Reaction notes

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