Methanamine, N-methoxy-, hydrochloride (1:1) → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

HRID 602441Notes

Reaction equation

HRID 602441 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].C(N(C(C)C)CC)(C)C.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25]([C:28]([OH:30])=O)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>CN(C)C=O.O>[CH3:5][O:4][N:3]([CH3:2])[C:28]([CH:25]1[CH2:24][CH2:23][N:22]([C:20]([O:19][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:21])[CH2:27][CH2:26]1)=[O:30]

Participants

6

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

Product 1

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateYield 110.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N,O-dimethylhydroxylamine hydrochloride (894 mg, 9.17 mmol), 2-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronio hexafluorphosphate (HBTU) (3.48 g, 9.17 mmol) and diisopropylethylamine (DIPEA) in N,N-dimethylformamide (40 mL) was carefully added 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (2 g, 8.73 mmol) and the reaction mixture was stirred at room temperature for 2 days. The mixture was diluted with water (200 mL), extracted with ethyl acetate, washed with aqueous citric acid 5%, aqueous sodium bicarbonate 4%, water, and brine and dried over sodium sulphate. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica flash, using ethyl acetate as eluent (isocratic), to yield the title compound (2.63 g, 99%) as yellowish oil.

Workup

  1. extractionextracted with ethyl acetate
  2. washwashed with aqueous citric acid 5%, aqueous sodium bicarbonate 4%, water, and brine
  3. dry with materialdried over sodium sulphate
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was purified by column chromatography on silica flash

Sources & evidence

ORD record
ord-dd6e5ccc1ceb49629427842ec61759dd
Source dataset
uspto-grants-2011_03
Patent number
US07906530B2

Reaction notes

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