Hydrochloric Acid → 1-Benzyloxycarbonyl-4-[methoxycarbonyl(ethylamino)]-piperidine

HRID 369111Notes

Reaction equation

HRID 369111 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([NH:17][C:18]([O:20][CH3:21])=[O:19])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:22](I)[CH3:23].[H-].[Na+].Cl>CN(C=O)C.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]([C:18]([O:20][CH3:21])=[O:19])[CH2:22][CH3:23])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 18677680Benzyl 4-(methoxycarbonylamino)piperidine-1-carboxylate

Product 1

HCID 186777251-Benzyloxycarbonyl-4-[methoxycarbonyl(ethylamino)]-piperidineYield 97%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To 82 mg (0.28 mmol) of 1-benzyloxycarbonyl-4-(methoxycarbonylamino)piperidine from Step A and 0.045 mL (0.56 mmol) of ethyl iodide in 4 mL of DMF under nitrogen was added 22 mg (0.56 mmol) of 60% sodium hydride in mineral oil. The reaction was stirred at rt for 1 h and was then poured into water containing 1 mL of 2 N hydrochloric acid and extracted twice with ether. The organic layers were each washed with a portion of brine, dried over sodium sulfate, combined and concentrated. The residue was purified by FCC eluting with 50% ethyl acetate/hexanes to afford 87 mg of title compound. 1H NMR (400 MHz, CDCl3): δ 1.07 (t, J=7, 3H), 1.5-1.8 (m, 4H), 2.79 (m, 2H), 3.15 (m, 2H), 3.68 (s, 3H), 4.10 (m, 1H), 4.26 (m, 2H), 5.10 (s, 2H), 7.34 (m, 5H).

Workup

  1. extractionextracted twice with ether
  2. washeach washed with a portion of brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by FCC
  6. washeluting with 50% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-58a0e08568b54a5ca974142a8513edd4
Source dataset
uspto-grants-2000_10
Patent number
US06136827

Reaction notes

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