Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 57959898, compound

HRID 1698500Notes

Reaction equation

HRID 1698500 reaction equation
C([Mg]Cl)(C)C.Cl.[CH3:7][NH:8][O:9][CH3:10].[CH:11]12[CH2:17][CH:14]([CH2:15][CH2:16]1)[CH:13]([C:18]([O:20]CC)=O)[N:12]2[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]>C1COCC1>[CH3:10][O:9][N:8]([CH3:7])[C:18]([CH:13]1[CH:14]2[CH2:17][CH:11]([CH2:16][CH2:15]2)[N:12]1[C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])=[O:20]

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 67275908HCID 67275908, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 57959898HCID 57959898, compoundYield 73.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Isopropylmagnesium chloride (41.3 mL of a 2 M solution in THF, 82.6 mmol) was added dropwise to a cooled 0° C. mixture of N,O-dimethylhydroxylamine hydrochloride (4.0 g, 41.3 mmol) and 2-tert-butyl 3-ethyl 2-azabicyclo[2.2.1]heptane-2,3-dicarboxylate (prepared according to procedures described in EP 947506) (7.9 g, 29.5 mmol) in THF (50 mL). The mixture was stirred for 30 min and quenched with saturated aqueous ammonium chloride (50 mL) and 33% aqueous ammonia (50 mL). The mixture was extracted into ethyl acetate (2×100 mL). The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified on silica gel eluting with iso-hexane on a gradient of ethyl acetate (0-60%) to give the title product (6.17 g, 73%). 1H NMR (400 MHz, CDCl3, δ 1:1 mixture of rotamers): δ 4.37 (0.5H, s), 4.24 (0.5H, s), 4.13 (0.5H, s), 4.06 (0.5H, s), 3.78-3.71 (3H, m), 3.21-3.19 (3H, m), 2.58 (1H, m), 2.10-2.00 (1H, m), 1.80-1.40 (4H, m), 1.44 (4.5H, s) and 1.39 (4.5H, m), 1.19 (1H, m).

Workup

  1. customquenched with saturated aqueous ammonium chloride (50 mL) and 33% aqueous ammonia (50 mL)
  2. extractionThe mixture was extracted into ethyl acetate (2×100 mL)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. concentrationconcentrated
  5. customThe residue was purified on silica gel eluting with iso-hexane on a gradient of ethyl acetate (0-60%)

Sources & evidence

ORD record
ord-d54796621b464e959292d5fd452873e6
Source dataset
uspto-grants-2012_04
Patent number
US08163956B2

Reaction notes

Loading…