Methanamine, N-methoxy-, hydrochloride (1:1) → 2-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylacetamide

HRID 2279449Notes

Reaction equation

HRID 2279449 reaction equation
[Si:1]([O:8][CH2:9][C:10]([O:12]CC)=O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].Cl.[CH3:16][NH:17][O:18][CH3:19].C([Mg]Cl)(C)C>C1COCC1>[Si:1]([O:8][CH2:9][C:10]([N:17]([O:18][CH3:19])[CH3:16])=[O:12])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 11183578Ethyl [(tert-butyldimethylsilyl)oxy]acetateHCID 178418918HCID 178418918, compound

Product 1

HCID 116010942-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylacetamideYield 70.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-(tert-butyldimethylsilyloxy)acetate (59, 20.0 g, 91.59 mmol), N,O-dimethylhydroxylamine hydrochloride (18.76 g, 192.3 mmol) and THF (800 mL) cooled to 0° C. was added dropwise via addition funnel isopropylmagnesium chloride (183.2 mL, 366.4 mmol) and the reaction was stirred for 3 h. The reaction was quenched with saturated NH4Cl and extracted with EtOAc. The organic layer was dried, filtered and concentrated. The crude product was purified by passage through a SiO2 plug eluting with 20% EtOAc/hexane to afford 15.12 g (70.7%) of 2-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylacetamide (60).

Workup

  1. customThe reaction was quenched with saturated NH4Cl
  2. extractionextracted with EtOAc
  3. customThe organic layer was dried
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by passage through a SiO2 plug
  7. washeluting with 20% EtOAc/hexane

Sources & evidence

ORD record
ord-bcd03079a51e47b889f3dd148533bd33
Source dataset
uspto-grants-2015_09
Patent number
US09133187B2

Reaction notes

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