Methanamine, N-methoxy-, hydrochloride (1:1) → (R)-3-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylbutanamide

HRID 1039650Notes

Reaction equation

HRID 1039650 reaction equation
C([Mg]Cl)(C)C.[Si:6]([O:13][C@H:14]([CH3:21])[CH2:15][C:16]([O:18]CC)=O)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[CH3:22][NH:23][O:24][CH3:25].Cl>C1COCC1>[Si:6]([O:13][C@H:14]([CH3:21])[CH2:15][C:16]([N:23]([O:24][CH3:25])[CH3:22])=[O:18])([C:9]([CH3:10])([CH3:11])[CH3:12])([CH3:7])[CH3:8]

Participants

5

Reactant 3

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 12914545Butanoic acid, 3-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-, ethyl ester, (3R)-HCID 178418918HCID 178418918, compound

Product 1

HCID 86676092(R)-3-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylbutanamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 2M isopropylmagnesium chloride in THF (800 mL, 1.60 mol) was added dropwise via cannula over 60 min to a stirred solution of (R)-ethyl 3-(tert-butyldimethylsilyloxy)butanoate (131 g, 532 mmol) and N,O-dimethylhydroxylamine/HCl (80 g, 824 mmol) in dry THF (850 mL) while maintaining the internal temperature between −30° C. and −20° C. The suspension was allowed to stir for 3 h between −20 and −10° C., and quenched while cold with saturated aqueous ammonium chloride solution (400 mL). The reaction mixture was partitioned between water (200 mL) and diethyl ether (500 mL) and the aqueous phase was further extracted with diethyl ether (1 L). The combined organic phases were washed with brine, dried over MgSO4, filtered, concentrated and dried under high vacuum to yield (R)-3-(tert-butyldimethylsilyloxy)-N-methoxy-N-methylbutanamide. The reaction was repeated 6 times to yield a total of 717 g material. The analytical data complied with data reported in the literature. The material was used without additional purification.

Workup

  1. temperaturewhile maintaining the internal temperature between −30° C. and −20° C
  2. customquenched while cold with saturated aqueous ammonium chloride solution (400 mL)
  3. customThe reaction mixture was partitioned between water (200 mL) and diethyl ether (500 mL)
  4. extractionthe aqueous phase was further extracted with diethyl ether (1 L)
  5. washThe combined organic phases were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-c7322076e5c14c5fba75e4651b2006d7
Source dataset
uspto-grants-2013_10
Patent number
US08552047B2

Reaction notes

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