Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 78148858, compound

HRID 218059Notes

Reaction equation

HRID 218059 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][CH:14]2[CH:10]([CH2:11][CH:12]([C:16]([OH:18])=O)[CH2:13]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[CH3:20][NH:21][O:22][CH3:23].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:23][O:22][N:21]([CH3:20])[C:16]([CH:12]1[CH2:11][CH:10]2[CH:14]([CH2:15][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9]2)[CH2:13]1)=[O:18]

Participants

7

Reactant 5

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 438109002-(tert-Butoxycarbonyl)octahydrocyclopenta[c]pyrrole-5-carboxylic acid

Product 1

HCID 78148858HCID 78148858, compoundYield 86.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]octane-7-carboxylic acid (0.930 g, 3.65 mmol), N,O-dimethylhydroxylamine hydrochloride (0.71 g, 7.3 mmol) and diisopropylethylamine (DIPEA) (3.24 mL, 18.3 mmol) in N,N-dimethylformamide (DMF) (50 mL) was added O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (2.07 g, 5.48 mmol), and the mixture was stirred at ambient temperature overnight. The reaction was poured into saturated aqueous sodium bicarbonate (100 mL) and extracted with ethyl acetate (100 mL). The organic layer was washed with water (200 mL), dried over anhydrous sodium sulfate, concentrated by rotary evaporation and purified by silica gel flash column chromatography, to obtain 0.94 g (86% yield) of the N-methoxy-N-methyl-3-(tert-butoxycarbonyl)-3-azabicyclo[3.3.0]octane-7-carboxamide, as an oil (1H NMR (CDCl3, 300 MHz): δ 3.69 (s, 3H), 3.6-3.42 (m, 2H), 3.36-3.05 (m, 3H), 3.18 (s, 3H), 2.82-2.57 (m, 2H), 2.08-2.02 (m, 2H), 1.82-1.65 (m, 2H), 1.46 (d, 9H); MS (m/z: 299 (M+1), 243 (M+1-56)).

Workup

  1. extractionextracted with ethyl acetate (100 mL)
  2. washThe organic layer was washed with water (200 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated by rotary evaporation
  5. custompurified by silica gel flash column chromatography

Sources & evidence

ORD record
ord-cf8d98f267c54c4ab1d3952cb2c3add1
Source dataset
uspto-grants-2012_06
Patent number
US08198296B2

Reaction notes

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