Sodium Carbonate → N-(tert-Butoxycarbonyl)-3-(dimethylamino)alanine

HRID 1783603Notes

Reaction equation

HRID 1783603 reaction equation
Cl.Cl.[NH2:3][CH:4]([C:9]([OH:11])=[O:10])[CH2:5][N:6]([CH3:8])[CH3:7].[C:12](O[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])(OC(C)(C)C)=O.C([O-])([O-])=O.[Na+].[Na+]>CC#N>[CH3:7][N:6]([CH3:8])[CH2:5][CH:4]([NH:3][CH3:12])[CH2:9][OH:11].[C:23]([O:22][C:20]([NH:3][CH:4]([CH2:5][N:6]([CH3:8])[CH3:7])[C:9]([OH:11])=[O:10])=[O:21])([CH3:24])([CH3:25])[CH3:26]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 90495Di-tert-butyl dicarbonateHCID 441345533-(Dimethylamino)alanine--hydrogen chloride (1/2)2×

Product 2

HCID 13850981N-(tert-Butoxycarbonyl)-3-(dimethylamino)alanineYield 31%HCID 64796328HCID 64796328, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

3-Dimethylamino-2-methylamino-propan-1-ol is prepared from 4-aza-DL-leucine 2 HCl. Di-tert-butyl dicarbonate (0.65 g, 2.97 mmol) is added to a biphasic mixture of 4-aza-DL-leucine 2 HCl (0.51 g, 2.47 mmol) in 10 ml 1:1 10% Na2CO3:MeCN. After stirring 16 hours, the MeCN is removed under reduced pressure and the aqueous layer is extracted with ethyl acetate. The aqueous layer is concentrated and purified by reverse phase column chromatography on a sep-pak C18 column (water) yielding 0.19 g (31%) 2-tert-butoxycarbonylamino-3-dimethylamino-propionic acid, sodium salt. The sodium salt is suspended in THF (5 ml) and cooled to 0° C. under N2. LAH (3.8 ml of a 1.0 M solution in THF) is added and the reaction mixture warmed to rt and than to reflux. After stirring at reflux for 16 h, the reaction mixture is cooled to 0° C. and carefully quenched by the slow addition of Na2SO4.10 H2O. The reaction mixture is diluted with diethyl ether, warmed to room temperature and stirred for 30 min. The gray suspension is filtered through Celite and the filtrate concentrated to give 83 mg (82%) of 3-dimethylamino-2-methylamino-propan-1ol as an oil.

Workup

  1. customthe MeCN is removed under reduced pressure
  2. extractionthe aqueous layer is extracted with ethyl acetate
  3. concentrationThe aqueous layer is concentrated
  4. custompurified by reverse phase column chromatography on a sep-pak C18 column (water)

Sources & evidence

ORD record
ord-87d9d2d9ebbd4c55aa6b5c61a5d99f8c
Source dataset
uspto-grants-2009_03
Patent number
US07501427B2

Reaction notes

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