Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 10538260, compound

HRID 1698502Notes

Reaction equation

HRID 1698502 reaction equation
C[Si](C=[N+]=[N-])(C)C.[CH3:8][C:9]([O:12][C:13]([N:15]1[C@H:18]([C:19]([OH:21])=O)[CH2:17][CH2:16]1)=[O:14])([CH3:11])[CH3:10].Cl.[CH3:23][NH:24][O:25][CH3:26].C([Mg]Cl)(C)C>CCOCC.C1COCC1.CO.ClCCl>[CH3:26][O:25][N:24]([CH3:23])[C:19]([C@@H:18]1[CH2:17][CH2:16][N:15]1[C:13]([O:12][C:9]([CH3:8])([CH3:10])[CH3:11])=[O:14])=[O:21]

Participants

9

Reactant 4

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 167693TrimethylsilyldiazomethaneHCID 2734495(2S)-1-((tert-butoxy)carbonyl)azetidine-2-carboxylic acidHCID 178418918HCID 178418918, compound

Product 1

HCID 10538260HCID 10538260, compoundYield 75%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of trimethylsilyldiazomethane in ether (2M, 9 mL) was added dropwise to a stirred, ice-bath cooled, mixture of 1-Boc-L-azetidine-2-carboxylic acid (3 g, 15 mmol), dichloromethane (20 mL) and methanol (5 mL) until yellow colour persisted. The mixture was concentrated in vacuo. The residue was treated with THF (30 mL) and N,O-dimethylhydroxylamine hydrochloride (2.04 g; 20.9 mmol) and cooled to 0° C. i-Propylmagnesium chloride in THF (2 M, 22.4 ml, 44.7 mmol) was added dropwise to the mixture and it was stirred for 30 min. After quenching with saturated aqueous NH4Cl (25 ml) and concentrated NH3 (25 ml), the mixture was extracted into ethyl acetate (150 mL). The organic extract was dried (Na2SO4) and concentrated. The residue was purified on silica gel (hexanes-ethyl acetate 0-100%) to give the title product (2.73 g, 75%). 1H NMR (500 MB, CDCl3): δ 5.03 (1H, m), 4.05 (1H, m), 3.87 (1H, m), 3.71 (3H, s), 3.22 (3H, s), 2.46 (1H, m), 2.13 (1H, m), 1.43 (9H, s).

Workup

  1. temperaturecooled
  2. concentrationThe mixture was concentrated in vacuo
  3. additionwas added dropwise to the mixture and it
  4. customAfter quenching with saturated aqueous NH4Cl (25 ml) and concentrated NH3 (25 ml)
  5. extractionthe mixture was extracted into ethyl acetate (150 mL)
  6. extractionThe organic extract
  7. dry with materialwas dried (Na2SO4)
  8. concentrationconcentrated
  9. customThe residue was purified on silica gel (hexanes-ethyl acetate 0-100%)

Sources & evidence

ORD record
ord-843b46bef3924f6aa2fe0906defcf897
Source dataset
uspto-grants-2012_04
Patent number
US08163956B2

Reaction notes

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