4-Methylmorpholine → tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylate

HRID 1063367Notes

Reaction equation

HRID 1063367 reaction equation
[C:1]([N:8]1[CH2:16][CH2:15][CH:11]([C:12]([OH:14])=O)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.[CH3:18][NH:19][O:20][CH3:21].CN1CCOCC1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>C(Cl)Cl>[C:4]([O:3][C:1]([N:8]1[CH2:9][CH2:10][CH:11]([C:12](=[O:14])[N:19]([O:20][CH3:21])[CH3:18])[CH2:15][CH2:16]1)=[O:2])([CH3:5])([CH3:6])[CH3:7]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid

Product 1

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateYield 105.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 30 g (130.9 mmol) of Boc-isonipecotic acid in 1.5 1 CH2Cl2 was treated with 20.42 g (209.3 mmol) of N,O-dimethylhydroxylamine hydrochloride, 23.1 ml (209.3 mmol) of N-methylmorpholine and at 0° C. with 32.6 g (170.1 mmol) of EDCI and 3.53 g (26.2 mmol) of HOBT. The reaction was stirred overnight at room temperature and partitioned between aqueous 10% KHSO4/Et2O (3×). The organic phases were washed with aqueous saturated NaHCO3, 10% NaCl and dried over Na2SO4 to give 37.54 g (quantitative) of 4-(methoxy-methyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester, MS: 273(MH+).

Workup

  1. custompartitioned between aqueous 10% KHSO4/Et2O (3×)
  2. washThe organic phases were washed with aqueous saturated NaHCO3, 10% NaCl
  3. dry with materialdried over Na2SO4

Sources & evidence

ORD record
ord-02744790451e40ada549b9b3ae61a97d
Source dataset
uspto-grants-2005_11
Patent number
US06964974B2

Reaction notes

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