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

HRID 1888205Notes

Reaction equation

HRID 1888205 reaction equation
Cl.[CH3:2][NH:3][O:4][CH3:5].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:39]([N:46]1[CH2:51][CH2:50][CH:49]([C:52](O)=[O:53])[CH2:48][CH2:47]1)([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40]>CN(C=O)C>[CH3:2][N:3]([O:4][CH3:5])[C:52]([CH:49]1[CH2:50][CH2:51][N:46]([C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[CH2:47][CH2:48]1)=[O:53]

Participants

6

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 11065582tert-Butyl 4-(methoxy(methyl)carbamoyl)piperidine-1-carboxylateYield 176.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,O-Dimethylhydroxylamine hydrochloride (4.26 g, 43.7 mmols), di-isopropylethylamine (33.88 g, 45.66 mL, 262.2 mmols) and HATU (19.94 g, 52.4 mmols) were added to a solution of N-Boc-piperidine-4-carboxylic acid (11.03 g, 48.1 mmols) in dry DMF (250 mL). The reaction mixture was stirred at room temperature for 72 hrs. The DMF was removed in vacuo and the residue was partitioned between ethyl acetate (200 mL) and saturated aqueous sodium bicarbonate (200 mL). The organic phase was separated, washed with saturated aqueous sodium bicarbonate (200 mL) and brine (200 mL), and dried over MgSO4. Evaporation of the solvent afforded a dark oil (21.0 g) that was purified by flash chromatography (Silica, gradient elution with pentane/ethyl acetate 9:1 v/v to 3:2 v/v) to give the title compound 12.5 g (95%) as a gum.

Workup

  1. customThe DMF was removed in vacuo
  2. customthe residue was partitioned between ethyl acetate (200 mL) and saturated aqueous sodium bicarbonate (200 mL)
  3. customThe organic phase was separated
  4. washwashed with saturated aqueous sodium bicarbonate (200 mL) and brine (200 mL)
  5. dry with materialdried over MgSO4
  6. customEvaporation of the solvent

Sources & evidence

ORD record
ord-183cb7d5d4b04dfe94b085bb3b0a9c43
Source dataset
uspto-grants-2013_08
Patent number
US08501780B2

Reaction notes

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