Methylamine → HCID 12151021, compound

HRID 380657Notes

Reaction equation

HRID 380657 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:14](O)=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[CH2:25][N:26]=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1.CN.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)([C:14](=[O:15])[NH:26][CH3:25])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 5

HCID 6329MethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 121510204-Benzyl-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid

Product 1

HCID 12151021HCID 12151021, compoundYield 93.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-tert-butyloxycarbonyl-4-benzylpiperidine-4-carboxylic acid (3.0 g; 9.0 mmol) was dissolved in methylene chloride (25 ml) and EDAC (1.8 g; 9.0 mmol) and HOAt (1.3 g; 9.0 mmol) was added. The mixture was stirred for 15 min, then methyl amine (33% in ethanol; 2.3 ml; 18 mmol) and DIEA (1.6 ml; 9.0 mmol) was added and the mixture was stirred overnight. Methylene chloride (100 ml) was added and the mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml) and a aqueous solution of sodium hydrogensulfate (10%, 50 ml), dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica (90 g) using a mixture of aqueous ammonia/ethanol/methylene chloride (1:7:92) as eluent to afford 2.8 g of 4-benzyl-4-methylcarbamoylpiperidine-1-carboxylic acid tert-butyl ester.

Workup

  1. stirringthe mixture was stirred overnight
  2. washthe mixture was washed with a saturated aqueous solution of sodium hydrogen carbonate (50 ml)
  3. dry with materiala aqueous solution of sodium hydrogensulfate (10%, 50 ml), dried (MgSO4)
  4. customevaporated in vacuo
  5. customThe residue was chromatographed on silica (90 g)
  6. additiona mixture of aqueous ammonia/ethanol/methylene chloride (1:7:92) as eluent

Sources & evidence

ORD record
ord-12ff3c28c96645d9abe26e9eef8aa027
Source dataset
uspto-grants-2001_10
Patent number
US06303620B1

Reaction notes

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